Med Chem [JOURNAL]
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200 papers
Extraction, Isolation and Purification of Catechins and their Applications.
Cao HM, Fang JJ, Zhao YT … +2 more , Zhao PH, Chen X
Med Chem · 2025 · PMID 39779576 · Publisher ↗
Catechins, the main active components of tea polyphenols, boast remarkable antioxidant activities because of their unique structures. This translates to a range of potential health benefits, including fighting antibacter...
Catechins, the main active components of tea polyphenols, boast remarkable antioxidant activities because of their unique structures. This translates to a range of potential health benefits, including fighting antibacterial, inflammation, and even cancers. However, extracting these beneficial compounds can be tricky as they're prone to degradation. Thankfully, recent advancements have yielded successful methods for isolating and purifying catechins, allowing us to obtain them in their purest form. The power of catechins isn't just theoretical. and studies have demonstrated promising results in treating various conditions like inflammation, cancer, neurodegenerative diseases, cardiovascular diseases, diabetes, and more. This review dives deep into the methods used to extract, isolate, and purify catechins. Additionally, it explores their potent antioxidant activities and exciting possibilities for future applications.
Synthesis, Antimicrobial Activity, DFT, Molecular Docking, and Dynamic Simulations of Trityl Mannopyranoside Derivatives for Potential Antibacterial Agents.
Akter S, Kawsar SMA, Bouzid G … +10 more , Horchani M, Bulbul MZH, Ghalla H, Jannet HB, Saha S, Fujii Y, Uddin KM, Bhat AR, Ahmed S, Ozeki Y
Med Chem · 2025 · PMID 39757636 · Publisher ↗
AIM: There is an urgent need for new antimicrobial compounds with alternative modes of action for the treatment of drug-resistant bacterial and fungal pathogens. BACKGROUND: Carbohydrates and their derivatives are essent...
AIM: There is an urgent need for new antimicrobial compounds with alternative modes of action for the treatment of drug-resistant bacterial and fungal pathogens. BACKGROUND: Carbohydrates and their derivatives are essential for biochemical and medicinal research because of their efficacy in the synthesis of biologically active drugs. OBJECTIVE: In the present study, a series of methyl α-D-mannopyranoside (MMP) derivatives (2-6) were prepared via direct acylation, and their biological properties were characterized. METHODS: The structures of synthesized compounds were established by analyzing their physicochemical, elemental, and spectroscopic data and evaluating their in vitro antimicrobial activities through studies. RESULTS: In the antibacterial study, compound 3 was found to be mostly active toward most of the organisms, exhibiting maximum inhibition of and minimum inhibition of . However, the MIC and MBC values revealed that this compound is highly effective against (MIC of 0.5 μg/L and MBC of 256 μg/L). In terms of antifungal activity, 3 and 6 showed the most promising activity toward , with an inhibition of 95.90 ± 1.0% for compound 3 and 96.72 ± 1.1% for compound 6. Moreover, density functional theory (DFT) in conjunction with the BLYP/6-311G (d) basis sets was used to calculate the dipole moment and total energy for each compound, and the molecular electrostatic potential and Mulliken charge were considered to study the electrophilicity and nucleophilicity of the groups in each compound. For dipole moment calculations, the dipole moments are in the following order: 6 < 3 < 1 < 5 < 2 < 4, inferring that compounds 2 and 4 possess a high dipole moment in comparison with the other inhibitor systems. Furthermore, molecular docking was performed against threonine synthase from ATCC 6633 (PDB: 6CGQ) to identify the active site of the compounds, with compound 3 showing a maximum binding energy of -10.3 kcal/mol and compound 4 exhibiting a binding energy of -10.2 kcal/mol. In addition, a 100 ns MD simulation was performed, and the results revealed a stable conformation and binding pattern within the stimulating environment. CONCLUSION: Our synthetic, antimicrobial, and in silico experiments revealed that MMP derivatives exhibit potential activity, providing a therapeutic target for bacteria and fungi.
Natural Products Inspired Drug Discovery for Infectious Diseases.
Upadhyay HC, Srivastava SK
Med Chem · 2024 · PMID 39105420 · Publisher ↗
Abstract loading — click title to view on PubMed.
A Computational Approach Using α-Carbonic Anhydrase to Find Anti- Agents.
Ortiz-Perez E, Mendez-Alvarez D, Juarez-Saldivar A … +9 more , Moreno-Rodríguez A, de Alba Alvarado M, Gonzalez-Gonzalez A, Vazquez K, Martinez-Vazquez AV, Nogueda-Torres B, Lara-Ramírez EE, Paz-Gonzalez AD, Rivera G
Med Chem · 2025 · PMID 39082172 · Publisher ↗
BACKGROUND: Chagas disease has an ineffective drug treatment despite efforts made over the last four decades. The carbonic anhydrase of (α-CA) has emerged as an interesting target for the design of new antiparasitic com...
BACKGROUND: Chagas disease has an ineffective drug treatment despite efforts made over the last four decades. The carbonic anhydrase of (α-CA) has emerged as an interesting target for the design of new antiparasitic compounds due to its crucial role in parasite processes. OBJECTIVE: The aim in this study was identify potential α-CA inhibitors with trypanocidal activity. METHODS: A maximum common substructure (MCS) and molecular docking were used to carried out a ligand- and structure-based virtual screening of ZINC20 and MolPort databases. The compounds selected were evaluated in an model against the NINOA strain of , and cytotoxicity was determined in a murine model of macrophage cells J774.2. RESULTS: Five sulfonamide derivatives (C7, C9, C14, C19, and C21) had the highest docking scores (-6.94 to -8.31 kcal/mol). They showed key residue interactions on the active site of the α-CA and good biopharmaceutical and pharmacokinetic properties. C7, C9, and C21 had half-maximal inhibitory concentration (IC) values of 26, 61.6, and 49 μM, respectively, against NINOA strain epimastigotes of . CONCLUSION: Compounds C7, C9, and C21 showed trypanocidal activity; therefore, these results encourage the development of new trypanocidal agents based in their scaffold.
and Activity of a New N-Oxide Derivative for Acne Vulgaris Treatment.
Delgado ILL, Scarim CB, Fernandes FHA … +9 more , Barbieri KP, Polesi MC, Pavan AR, Chiba DE, Salgado HRN, Carlos IZ, Correa MA, de Andrade CR, Dos Santos JL
Med Chem · 2025 · PMID 39082171 · Publisher ↗
INTRODUCTION: Furoxan and benzofuroxan are compounds containing an -oxide function, known for their diverse pharmacological properties, including antimicrobial and antiinflammatory effects. This study aimed to investigat...
INTRODUCTION: Furoxan and benzofuroxan are compounds containing an -oxide function, known for their diverse pharmacological properties, including antimicrobial and antiinflammatory effects. This study aimed to investigate these activities using an in-house library of N-oxide compounds. METHOD: Twenty compounds were tested against both Gram-positive and Gram-negative bacteria, including , a microorganism implicated in the development of acne vulgaris. One compound, (E)-4-(3-((2-(3-hydroxybenzoyl)hydrazone)methyl)phenoxy)-3- (phenylsulfonyl)-1,2,5-oxadiazol-2-N-oxide (compound 15), exhibited selective antimicrobial activity against , with a Minimum Inhibitory Concentration (MIC) value of 2 μg/mL. Indirect measurement of Nitric Oxide (NO) release showed that compound 15 and isosorbide dinitrate, when treated with , produced nitrite levels of 20.1% and 9.95%, respectively. Using a NO scavenger (PTIO) in combination with compound 15 in a culture of resulted in reduced antimicrobial activity, indicating that NO release is part of its mechanism of action. Cytotoxicity assessments using murine macrophages showed cellular viability above 70% at concentrations up to 0.78 μg/mL. RESULTS: Measurements of Interleukin-1 beta (IL1-β) and Tumor Necrosis Factor-alpha (TNF-α) indicated that compound 15 did not reduce the levels of these pro-inflammatory cytokines. Sustained NO production by inducible Nitric Oxide Synthase (iNOS) in macrophages or neutrophils has been found to be involved in the inflammatory process in acne vulgaris and lead to toxicity in surrounding tissues. Nitrite levels in the supernatant of murine macrophages were found to be decreased at a concentration of 0.78 μg/mL of compound 15, indicating an anti-inflammatory effect. studies were conducted using Balb/c nude mice inoculated subcutaneously with Cream and gel formulations of compound 15 were applied to treat the animals, along with commercially available anti-acne drugs, for 14 days. Animals treated with a cream base containing 5% of compound 15 exhibited less acanthosis with mild inflammatory infiltration compared to other groups, highlighting its anti-inflammatory properties. CONCLUSION: Similar results were observed in the benzoyl peroxide group, demonstrating that compound 15 presented comparable anti-inflammatory activity to the FDA-approved drug. These promising results suggest that compound 15 has a dual mechanism of action, with selective antimicrobial activity against and notable anti-inflammatory properties, making it a potential prototype for developing new treatments for acne vulgaris.
-Disubstituted 4-Sulfamoylbenzoic Acid Derivatives as Inhibitors of Cytosolic Phospholipase A: Synthesis, Aqueous Solubility, and Activity in a Vesicle and a Whole Blood Assay.
Borecki D, Vilsendorf IMZ, Fabian J … +1 more , Lehr M
Med Chem · 2024 · PMID 39041279 · Publisher ↗
BACKGROUND: Cytosolic phospholipase A2α (cPLA) is the key enzyme that initiates the arachidonic acid cascade through which pro-inflammatory lipid mediators can be formed. Therefore, cPLA is considered an interesting targ...
BACKGROUND: Cytosolic phospholipase A2α (cPLA) is the key enzyme that initiates the arachidonic acid cascade through which pro-inflammatory lipid mediators can be formed. Therefore, cPLA is considered an interesting target for the development of anti-inflammatory drugs. Although several effective inhibitors of the enzyme have been developed, none of them has yet reached clinical application. OBJECTIVE: Recently, we have prepared new 4-sulfamoylbenzoic acid derivatives based on a cPLA inhibitor found in a ligand-based virtual screening. The most effective of these compounds were now subjected to further variations in which the substitution pattern on the sulfamoyl nitrogen atom was changed.. METHODS: The new compounds were tested in a vesicle assay for cPLA inhibition as well as for their water solubility, metabolic stability, and selectivity towards related enzymes. In addition, they were evaluated in a whole blood assay in which metabolites of the arachidonic acid cascade formed after activation of cPLA were quantified using a combined online dilution/ online solid phase extraction HPLC-MS method. RESULTS: Inhibitors with submicromolar inhibitory potency were found with favourable water solubility and selectivity. However, their efficacy did not match that of the highly effective, known, structurally related cPLA inhibitor giripladib, which was also tested as a reference. One advantage of some of the new compounds compared to giripladib was their significantly improved water solubility. When analyzing the substances in the whole blood assay, it was found that the obtained inhibition data correlated better with the results when the phorbol ester 12-Otetradecanoylphorbol- 13-acetate was used for activation of the enzyme in the blood cells instead of the calcium ionophore A23187. CONCLUSION: New compounds with good activity towards cPLA and reasonable physicochemical properties were identified. Overall, the results obtained could be helpful in the development of clinically applicable inhibitors of this enzyme.
Chemically Synthesized 1,2,3,4,6-Pentakis-O-Galloyl-β-D-Glucopyranoside Blocks SARS-CoV-2 Spike Interaction with Host ACE-2 Receptor.
Ezell J, Al-Horani RA
Med Chem · 2024 · PMID 39041278 · Full text
BACKGROUND: In the search for anti-COVID-19 therapy, 1,2,3,4,6-pentakis-O-galloyl-β- D-glucopyranoside, a natural polyphenolic compound isolated from many traditional medicinal herbs, has been reported as an RBD-ACE2 bin...
BACKGROUND: In the search for anti-COVID-19 therapy, 1,2,3,4,6-pentakis-O-galloyl-β- D-glucopyranoside, a natural polyphenolic compound isolated from many traditional medicinal herbs, has been reported as an RBD-ACE2 binding inhibitor and as a broad-spectrum anticoronaviral inhibitor targeting the main protease and RNA-dependent RNA polymerase of SARSCoV- 2. To facilitate the structure-activity relationship studies of 1,2,3,4,6-pentakis-O-galloyl-β-Dglucopyranoside, we describe its chemical synthesis and characterization, as well as its activity towards the SARS-CoV-2 spike interaction with host ACE2 receptor. METHODS: 1,2,3,4,6-Pentakis-O-galloyl-β-D-glucopyranoside was synthesized in two quantitative steps from 3,4,5-tribenzyloxybenzoic acid and β-D-glucopyranoside: DCC-mediated esterification and palladium-catalyzed per-debenzylation. The synthesized molecule was evaluated using a SARS-CoV-2 spike trimer (S1 + S2) ACE2 inhibitor screening colorimetric assay kit, SARS-CoV- 2 spike S1 RBD ACE2 inhibitor screening assay kit, and a cellular neutralization assay using the Spike (SARS-CoV-2) Pseudotyped Lentivirus, ACE2-HEK293 recombinant cell line. RESULTS: The chemically synthesized product blocked the binding of the spike trimer of SARSCoV- 2 to the human ACE2 receptor with IC=22±2 μM. It also blocked ACE2: spike RBD binding with IC=27±3 μM. Importantly, it inhibited the infectivity of SARS2-CoV2-Spike pseudotyped lentivirus on the ACE2 HEK293 cell line with IC=20±2 μM. CONCLUSION: Overall, the chemically synthesized 1,2,3,4,6-pentakis-O-galloyl-β-D-glucopyranoside represents a lead molecule to develop anti-SARS-CoV-2 therapies that block the initial stage of the viral infection by blocking the virus entry to the host cell.
Crucial Structural Understanding for Selective HDAC8 Inhibition: Common Pharmacophores, Molecular Docking, Molecular Dynamics, and Zinc Binder Analysis of Selective HDAC8 Inhibitors.
Sarkar K, Debnath S, Sen D … +2 more , Kar S, Sil SK
Med Chem · 2025 · PMID 39039678 · Publisher ↗
BACKGROUND: Overexpression of HDAC8 was observed in various cancers and inhibition of HDAC8 has emerged as a promising therapeutic approach in recent decades. OBJECTIVE: This review aims to facilitate the discovery of no...
BACKGROUND: Overexpression of HDAC8 was observed in various cancers and inhibition of HDAC8 has emerged as a promising therapeutic approach in recent decades. OBJECTIVE: This review aims to facilitate the discovery of novel selective HDAC8 inhibitors by analyzing the structural scaffolds of 66 known selective HDAC8 inhibitors, along with their IC50 values against HDAC8 and other HDACs. METHODS: The inhibitors were clustered based on structural symmetry, and common pharmacophores for each cluster were identified using Phase. Molecular docking with all HDACs was performed to determine binding affinity and crucial interacting residues for HDAC8 inhibition. Representative inhibitors from each cluster were subjected to molecular dynamics simulation to analyze RMSD, RMSF, active site amino acid residues, and crucial interacting residues responsible for HDAC8 inhibition. The study reviewed the active site amino acid information, active site cavities of all HDACs, and the basic structure of Zn binding groups. RESULTS: Common pharmacophores identified included AADHR_1, AADDR_1, ADDR_1, ADHHR_1, and AADRR_1. Molecular docking analysis revealed crucial interacting residues: HIS- 142, GLY-151, HIS-143, PHE-152, PHE-208 in the main pocket, and ARG-37, TYR-100, TYR- 111, TYR-306 in the secondary pocket. The RMSD of protein and RMSF of active site amino acid residues for stable protein-ligand complexes were less than 2.4 Å and 1.0 Å, respectively, as identified from MD trajectories. The range of Molecular Mechanics Generalized Born Surface Area (MM-GBSA) ΔG predicted from MD trajectories was between -15.8379 Å and -61.5017 Å kcal/mol. CONCLUSION: These findings may expedite the rapid discovery of selective HDAC8 inhibitors subject to experimental evaluation.
Synthesis and Biological Evaluation of Amino Acid and Peptide Conjugates of 5-Bromovaleric Acid.
Kumar S, Kaur H, Kumar S … +2 more , Verma N, Singh RK
Med Chem · 2024 · PMID 38982919 · Publisher ↗
BACKGROUND: Among various carboxylic acid derivatives, valeric acid or pentanoic acid is found to be widely distributed in nature. It is a straight-chain alkyl carboxylic acid containing five carbon atoms. Due to the the...
BACKGROUND: Among various carboxylic acid derivatives, valeric acid or pentanoic acid is found to be widely distributed in nature. It is a straight-chain alkyl carboxylic acid containing five carbon atoms. Due to the therapeutic value of valeric acid, it is used as a versatile nucleus in the pharmaceutical field. Valeric acid derivatives are associated with a broad spectrum of biological activities, like anticonvulsant, antiplatelet, antidiabetic, and plant growth activities. AIM: It has previously been revealed that peptide derivatives of carboxylic acids are accountable for enhanced antimicrobial activity. Therefore, it was hypothesized that coupling peptides with valeric acid would increase the antimicrobial properties of the target compounds. So, the objective of the present study was to synthesize peptide derivatives of 5-bromovaleric acid and evaluate their antibacterial and antifungal activities. METHODS: 5-bromovaleric acid was synthesized by the reaction of cyclopentanone and hydrogen peroxide in the presence of copper bromide and sodium bromide. Additionally, 5-bromovaleric acid was coupled with amino acid methyl esters, dipeptides, tripeptides, and tetrapeptides in the presence of dicyclohexylcarbodimide (DCC) and N-methylmorpholine (NMM) as a base under continuous stirring for 36 hours to produce its peptide derivatives. RESULTS: The results obtained showed that 5-bromovaleric acid possesses more potent antibacterial activity than N-terminal 5-bromovaleric acid conjugates of selected di-, tri, and tetra peptide Cterminal methyl esters against ciprofloxacin as a standard. The selected dipeptide and tripeptide Nterminal 5-bromovaleric acid-conjugated C-terminal methyl ester derivatives were more active than the selected tetrapeptide methyl ester analogue. Using fluconazole as a reference, the antifungal efficacy of 5-bromovaleric acid against and declined as it was combined with C-terminal methyl esters of selected dipeptides, tripeptides, and tetrapeptides. CONCLUSION: The novel selected peptide derivatives had less antibacterial and antifungal action than the parent 5-bromovaleric acid. Antibacterial and antifungal investigations showed that 5- bromopentanoic acid peptide derivatives might impair antimicrobial efficacy. Further, attaching 5- bromopentanoic acid to di, tri, and tetra peptides did not boost their antibacterial potential.
An Overview of the Pharmacological Activities and Synthesis of Benzothiophene Derivatives.
Pathak S, Singh AP, Sharma R … +1 more , Pandey R
Med Chem · 2024 · PMID 38920062 · Publisher ↗
One important class of organic compounds having many uses, especially in medical chemistry, is benzothiophene and its derivatives. This review examines the biological activity of benzothiophene derivatives and summarizes...
One important class of organic compounds having many uses, especially in medical chemistry, is benzothiophene and its derivatives. This review examines the biological activity of benzothiophene derivatives and summarizes the synthetic methods used in their production. The effectiveness of several synthetic pathways, such as cyclization techniques, functional group modifications, and reactions catalyzed by transition metals, in gaining access to benzothiophene scaffolds has been examined. Additionally, a broad spectrum of therapeutic domains, such as antiinflammatory, antibacterial, antidiabetic, anticancer, antimicrobial, anti-leishmanial, antifungal, antimalarial, and antitubercular activities, are covered by the pharmacological activities that are being explored. The synthesis and pharmacological potential of benzothiophene derivatives are well-explained in this thorough review, which opens up new options for medicinal chemistry and drug discovery study. Overall, this study is a useful resource for scientists working on drug development and discovery as it sheds light on the pharmacological potential of benzothiophene derivatives. This review includes the synthesis and bioactivities of the years 2002-2024. The goal of this review is to compile the existing information on benzothiophene derivatives and provide guidance for future research and development as well as insights into their possible medicinal uses.
The Catalysts-Based Synthetic Approaches to Quinolines: A Review.
Tripathi S, Kumar R, Mazumder A … +4 more , Salahuddin, Kukreti N, Kumar A, Singh S
Med Chem · 2024 · PMID 38918990 · Publisher ↗
The most common heterocyclic aromatic molecule with potential uses in industry and medicine is quinoline. Its chemical formula is C9H7N, and it has a distinctive double-ring structure with a pyridine moiety fused with a...
The most common heterocyclic aromatic molecule with potential uses in industry and medicine is quinoline. Its chemical formula is C9H7N, and it has a distinctive double-ring structure with a pyridine moiety fused with a benzene ring. Various synthetic approaches synthesize quinoline derivatives. These approaches include solvent-free synthetic approach, mechanochemistry, ultrasonic, photolytic synthetic approach, and microwave and catalytic synthetic approaches. One of the important synthetic approaches is a catalyst-based synthetic approach in which different catalysts are used such as silver-based catalysts, titanium-based nanoparticle catalysts, new iridium catalysts, barium-based catalysts, iron-based catalysts, gold-based catalysts, nickel-based catalyst, some metal-based photocatalyst, α-amylase biocatalyst, by using multifunctional metal-organic framework-metal nanoparticle tandem catalyst etc. In the present study, we summarized different catalyst-promoted reactions that have been reported for the synthesis of quinoline. Hopefully, the study will be helpful for the researchers.
Design, Synthesis and Evaluation of Antifungal Activity of Pyrazoleacetamide Derivatives.
Kachi OG, Pawar HR, Chabukswar AR … +6 more , Jagdale S, Swamy V, Vinayak K, Hingane D, Shinde M, Pawar N
Med Chem · 2024 · PMID 38867538 · Publisher ↗
BACKGROUND: Fungal infections have posed a big challenge in the management of their treatment. Due to the resistance and toxicity of existing drug molecules in the light of pandemic infections, like COVID-19, there is an...
BACKGROUND: Fungal infections have posed a big challenge in the management of their treatment. Due to the resistance and toxicity of existing drug molecules in the light of pandemic infections, like COVID-19, there is an urgent need to find newer derivatives of active molecules, which can be effective in fungal infections. OBJECTIVE: In the present study, we aimed to design pyrazole derivatives using molecular modeling studies against target 1EA1 and synthesize 10 molecules of pyrazole derivatives using a multi-step synthesis approach. METHODS: Designed pyrazole derivatives were synthesized by conventional organic methods. The newly synthesized pyrazole molecules were characterized by using FT-IR, HNMR, CNMR, and LC-MS techniques. Molecular docking studies were also performed. The antifungal activity of newly synthesized compounds was assessed against using the well plate method. RESULTS: Two of the compounds, OK-7 and OK-8, have been found to show significant docking interaction with target protein 1EA1. These two compounds have also been found to show significant anti-fungal activity against and when compared to the standard fluconazole. The Minimum Inhibitory Concentration (MIC) value of these two compounds has been found to be 50 μg/ml. CONCLUSION: Pyrazole derivatives with -CH, CHO-, and -CN groups have been found to be active against tested fungi and can be further explored for their potential as promising anti-fungal agents for applications in the field of medicinal chemistry.
and Assessment of Dimeric Flavonoids (Brachydins) on Glutathione S-transferase.
Dos Santos Bezerra WA, Tavares CP, Lima VAS … +5 more , da Rocha CQ, da Silva Vaz Junior I, Michels PAM, Costa Junior LM, Dos Santos Soares AM
Med Chem · 2024 · PMID 38847259 · Publisher ↗
INTRODUCTION: , an important cattle ectoparasite, is responsible for a substantial negative impact on the economy due to productivity loss. The emergence of resistance to widely used commercial acaricides has sparked eff...
INTRODUCTION: , an important cattle ectoparasite, is responsible for a substantial negative impact on the economy due to productivity loss. The emergence of resistance to widely used commercial acaricides has sparked efforts to explore alternative products for tick control. METHODS: To address this challenge, innovative solutions targeting essential tick enzymes, like glutathione S-transferase (GST), have gained attention. Dimeric flavonoids, particularly brachydins (BRAs), have demonstrated various biological activities, including antiparasitic effects. The objectives of this study were to isolate four dimeric flavonoids from roots and to evaluate their potential as inhibitors of GST. RESULTS: assays confirmed the inhibition of GST by BRA-G, BRA-I, BRA-J, and BRA-K with IC values of 0.075, 0.079, 0.075, and 0.058 mg/mL, respectively, with minimal hemolytic effects. Molecular docking of BRA-G, BRA-I, BRA-J, and BRA-K in a threedimensional model of GST revealed predicted interactions with MolDock Scores of - 142.537, -126.831, -108.571, and -123.041, respectively. Both and analyses show that brachydins are potential inhibitors of GST. CONCLUSION: The findings of this study deepen our understanding of GST inhibition in ticks, affirming its viability as a drug target. This knowledge contributes to the advancement of treatment modalities and strategies for improved tick control.
Targeting Diabetes with Azole-derived Medicinal Agents.
Mehra A
Med Chem · 2024 · PMID 38840402 · Publisher ↗
Azoles have long been regarded as an ideal scaffold for the development of numerous innovative therapeutic agents as well as other incredibly adaptable and beneficial chemicals with prospective uses in a variety of field...
Azoles have long been regarded as an ideal scaffold for the development of numerous innovative therapeutic agents as well as other incredibly adaptable and beneficial chemicals with prospective uses in a variety of fields, including materials, energetics (explosophores), and catalysis (azole organocatalytic arbitration). Azoles exhibit promising pharmacological activities, including antimicrobial, antidiabetic, antiviral, antidepressant, antihistaminic, antitumor, antioxidant, antiallergic, antihelmintic, and antihypertensive activity. According to a database analysis of U.S. FDAapproved medications, 59% of specific medications are connected to small molecules that have heterocycles having nitrogen atoms. The azole moiety has impressive electron abundance. Azoles promptly attach to various receptors as well as enzymes in the physiological environment via distinct specialized interactions, contributing to their anti-diabetic potential. This review encompasses the recent research progress on potent azole-derived antidiabetic agents that can be used as an alternative for the management of type-2 diabetes.
New 3-Hydroxypyridine-4-one Analogues: Their Synthesis, Antimicrobial Evaluation, Molecular Docking, and ADME Prediction.
Sadeghian S, Zare F, Saghaie L … +3 more , Fassihi A, Zare P, Sabet R
Med Chem · 2024 · PMID 38840401 · Publisher ↗
INTRODUCTION: Drug resistance to existing antimicrobial drugs has become a serious threat to human health, which highlights the need to develop new antimicrobial agents. METHODS: In this study, a new set of 3-hydroxypyri...
INTRODUCTION: Drug resistance to existing antimicrobial drugs has become a serious threat to human health, which highlights the need to develop new antimicrobial agents. METHODS: In this study, a new set of 3-hydroxypyridine-4-one derivatives (6a-j) was synthesized, and the antimicrobial effects of these derivatives were evaluated against a variety of microorganisms using the microdilution method. The antimicrobial evaluation indicated that compound 6c, with an electron-donating group -OCH at the meta position of the phenyl ring, was the most active compound against and species with an MIC value of 32 μg/mL. Compound 6c was more potent than ampicillin as a reference drug. RESULTS: The antifungal results showed that the studied derivatives had moderate effects (MIC = 128-512 μg/mL) against and species. The molecular modeling studies revealed the possible mechanism and suitable interactions of these derivatives with the target protein. CONCLUSION: The obtained biological results offer valuable insights into the design of more effective antimicrobial agents.
Efficient Synthesis of Mannopyranoside-based Fatty Acyl Esters: Effects of Acyl Groups on Antimicrobial Potential.
Rahaman ML, Rahman MA, Hasnain MM … +6 more , Amran M, Bin Emran T, Khan MAR, Patwary MAM, Kazi M, Matin MM
Med Chem · 2025 · PMID 38840400 · Publisher ↗
BACKGROUND: The approval of Sucrose Fatty Acid Esters (SFAEs) as food additives/ preservatives with antimicrobial potential has triggered enormous interest in discovering new biological applications. Accordingly, many re...
BACKGROUND: The approval of Sucrose Fatty Acid Esters (SFAEs) as food additives/ preservatives with antimicrobial potential has triggered enormous interest in discovering new biological applications. Accordingly, many researchers reported that SFAEs consist of various sugar moieties, and hydrophobic side chains are highly active against certain fungal species. OBJECTIVE: This study aimed to conduct aregioselective synthesis of SAFE and check the effect of chain length and site of acylation (i.e., C-6 vs. C-2, C-3, C-4, and long-chain vs. short-chain) on antimicrobial potency. METHODS: A direct acylation method maintaining several conditions was used for esterification. tests, molecular docking, and in silico studies were conducted using standard procedures. RESULTS: tests revealed that the fatty acid chain length in mannopyranoside esters significantly affects the antifungal activity, where C12 chains are more potent against Aspergillus species. In terms of acylation site, mannopyranoside esters with a C8 chain substituted at the C-6 position are more active in antifungal inhibition. Molecular docking also revealed that these mannopyranoside esters had comparatively better stable binding energy and hence better inhibition, with the fungal enzymes lanosterol 14-alpha-demethylase (3LD6), urate oxidase (1R51), and glucoamylase (1KUL) than the standard antifungal drug fluconazole. Additionally, the thermodynamic, orbital, drug-likeness, and safety profiles of these mannopyranoside esters were calculated and discussed, along with the Structure-Activity Relationships (SAR). CONCLUSION: This study thus highlights the importance of the acylation site and lipid-like fatty acid chain length that govern the antimicrobial activity of mannopyranoside-based SFAE.
Discovery and Predictive Modeling of Novel Acetylcholinesterase (AChE) Inhibitors for Alzheimer's Treatment.
Suha HN, Hossain MS, Rahman S … +5 more , Alodhayb AN, Hossain MM, Kawsar SMA, Poirier RA, Uddin KM
Med Chem · 2025 · PMID 38803179 · Publisher ↗
INTRODUCTION: Alzheimer's disease, akin to coronary artery disease of the heart, is a progressive brain disorder driven by nerve cell damage. METHODS: This study utilized computational methods to explore 14 anti-acetylch...
INTRODUCTION: Alzheimer's disease, akin to coronary artery disease of the heart, is a progressive brain disorder driven by nerve cell damage. METHODS: This study utilized computational methods to explore 14 anti-acetylcholinesterase (AChE) derivatives (1 ̶ 14) as potential treatments. By scrutinizing their interactions with 11 essential target proteins (AChE, Aβ, BChE, GSK-3β, MAO B, PDE-9, Prion, PSEN-1, sEH, Tau, and TDP-43) and comparing them with established drugs such as donepezil, galantamine, memantine, and rivastigmine, ligand 14 emerged as notable. During molecular dynamics simulations, the protein boasting the strongest bond with the critical 1QTI protein and exceeding drug-likeness criteria also exhibited remarkable stability within the enzyme's pocket across diverse temperatures (300- 320 K). In addition, we utilized density functional theory (DFT) to compute dipole moments and molecular orbital properties, including assessing the thermodynamic stability of AChE derivatives. RESULT: This finding suggests a well-defined, potentially therapeutic interaction further supported by theoretical and future and investigations. CONCLUSION: Ligand 14 thus emerges as a promising candidate in the fight against Alzheimer's disease.
New Thieno[2,3-d]pyrimidines as Anticancer VEGFR-2 Inhibitors with Apoptosis Induction: Design, Synthesis, and Biological and Studies.
Sobh EA, Dahab MA, Elkaeed EB … +4 more , Alsfouk BA, Ibrahim IM, Metwaly AM, Eissa IH
Med Chem · 2024 · PMID 38798211 · Publisher ↗
BACKGROUND: Vascular endothelial growth factor receptor-2 (VEGFR-2) is a critical protein involved in tumor progression, making it an attractive target for cancer therapy. OBJECTIVE: This study aimed to synthesize and ev...
BACKGROUND: Vascular endothelial growth factor receptor-2 (VEGFR-2) is a critical protein involved in tumor progression, making it an attractive target for cancer therapy. OBJECTIVE: This study aimed to synthesize and evaluate novel thieno[2,3-d]pyrimidine analogues as potential anticancer VEGFR-2 inhibitors. METHODS: The thieno[2,3-]pyrimidine analogues were synthesized following the pharmacophoric features of VEGFR-2 inhibitors. The anticancer potential was assessed against PC3 and HepG2 cell lines. The VEGFR-2 inhibition was evaluated through IC determination. Cell cycle analysis and apoptosis assays were performed to elucidate the mechanisms of action. Molecular docking, molecular dynamics simulations, MM-GBSA, and PLIP studies were conducted to investigate the binding affinities and interactions with VEGFR-2. Additionally, ADMET studies were performed. RESULTS: Compound 8b demonstrated significant anti-proliferative activities with IC values of 16.35 μM and 8.24 μM against PC3 and HepG2 cell lines, respectively, surpassing sorafenib and exhibiting enhanced selectivity indices. Furthermore, compound 8b showed an IC value of 73 nM for VEGFR-2 inhibition. Cell cycle analysis revealed G2-M phase arrest, while apoptosis assays demonstrated increased apoptosis in HepG2 cells. Molecular docking and dynamic simulations confirmed the binding affinity and interaction of compound 8b with VEGFR-2, supported by MMGBSA and PLIP studies. ADMET studies indicated the drug development potential of the synthesized thieno[2,3-]pyrimidines. CONCLUSION: The study highlights compound 8b as a promising VEGFR-2 inhibitor with potent anti-proliferative activities. Its mechanism of action involves cell cycle arrest and induction of apoptosis. Further, molecular docking and dynamic simulations support the strong binding affinity of compound 8b to VEGFR-2.
and Biological Activity of Two Aryloxy-naphthoquinones in Mice Infected with Strains.
Vázquez K, Moreno-Rodríguez A, Domínguez-Díaz LR … +5 more , Bertrand J, Salas CO, Rivera G, Cervera YP, Bocanegra-García V
Med Chem · 2024 · PMID 38757318 · Publisher ↗
BACKGROUND: Chagas disease, a condition caused by Trypanosoma cruzi, is an endemic disease in Latin American countries that affects approximately eight million people worldwide. It is a continuing public health problem....
BACKGROUND: Chagas disease, a condition caused by Trypanosoma cruzi, is an endemic disease in Latin American countries that affects approximately eight million people worldwide. It is a continuing public health problem. As nifurtimox and benznidazole are the two pharmacological treatments currently used to treat it, the present research proposes new therapeutic alternatives. Previous studies conducted on naphthoquinone derivatives have found interesting trypanocidal effects on epimastigotes, with the molecules 2-phenoxy-1,4-naphthoquinone (IC= 50 nM and SI < 250) and 2-(3-nitrophenoxy)-naphthalene-1,4-dione (IC= 20 nM and SI=625) presenting the best biological activity.. METHODS: The present study evaluated the efficacy of and in vivo models of two aryloxyquinones, 2-phenoxy-1,4-naphthoquinone (1) and 2-(3-nitrophenoxy)-naphthalene-1,4- dione (2), against two Mexican strains in both their epimastigote and blood Trypomastigote stage. Both compounds were evaluated against using a mouse model (CD1) infected with Mexican isolates of , nifurtimox and benznidazole used as control drugs. Finally, the cytotoxicity of the two compounds against the J774.2 mouse macrophage cell line was also determined. RESULTS: The and results obtained indicated that both quinones were more active than the reference drugs. Compound 1 presents in vivo activity, showing up to 40% parasite reduction after 8 h of administration, a finding which is 1.25 times more effective than the results obtained using nifurtimox. CONCLUSION: These are encouraging results for proposing new naphthoquinone derivatives with potential anti- activity.
Pyrazole Paradigms: Unveiling Synthetic Pathways and Unraveling Anti-Cancer Potential.
Kumari P, Agrawal N, Mujwar S
Med Chem · 2024 · PMID 38757317 · Publisher ↗
This review investigates the synthetic methods and anti-cancer activities of pyrazole compounds. Various synthetic approaches, including traditional organic synthesis and microwaveassisted synthesis, have been used to ch...
This review investigates the synthetic methods and anti-cancer activities of pyrazole compounds. Various synthetic approaches, including traditional organic synthesis and microwaveassisted synthesis, have been used to change the pyrazole core structure, resulting in new compounds with improved pharmacological properties. The paper also covers the mechanisms of action that underpin pyrazole derivatives' anti-cancer characteristics, focusing on interactions with major molecular targets implicated in cancer growth and proliferation. SAR insights help to rationally develop novel anti-cancer drugs. In conclusion, the review emphasizes the versatility of pyrazole derivatives as scaffolds for the discovery and development of new anti-cancer medicines. By understanding synthesis routes and unravelling anti-cancer potential, this study hopes to encourage new research endeavours focused on leveraging the therapeutic advantages of pyrazole paradigms in the fight against cancer.
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