Future Med Chem [JOURNAL]
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200 papers
Design, synthesis, and biological evaluation of novel coumarine-1,2,3-triazole hybrids as dual DNA gyrase/superoxide dismutase inhibitors: molecular docking, DFT, and ADMET investigations.
Patel GB, Bhola YO, Dholaria PV … +2 more , Suthar AR, Bhatt DM
Future Med Chem · 2026 Jun · PMID 42087833 · Full text
A series of eight novel coumarin-1,2,3-triazole hybrid derivatives were synthesized and evaluated for their antimicrobial and antioxidant potentials through and approaches. Molecular docking studies against DNA gyrase...
A series of eight novel coumarin-1,2,3-triazole hybrid derivatives were synthesized and evaluated for their antimicrobial and antioxidant potentials through and approaches. Molecular docking studies against DNA gyrase subunit B (PDB ID: 7P2M) revealed that compounds and exhibited superior-binding affinities with docking scores of -5.448 and -5.106 kcal/mol, respectively, surpassing ciprofloxacin (-4.992 kcal/mol). Against superoxide dismutase [Cu-Zn] (PDB ID: 1PU0), compound showed the highest binding affinity (-4.157 kcal/mol), comparable to ascorbic acid (-3.787 kcal/mol). Antimicrobial screening demonstrated that compound displayed potent broad-spectrum activity with MIC values of 50-100 µg/mL against , , , and . Antioxidant evaluation using the DPPH assay showed compound exhibited the highest activity (IC = 54.89 ± 1.2 µg/mL), approaching ascorbic acid (52.66 ± 0.8 µg/mL). DFT calculations for compound revealed favorable electronic properties with a HOMO-LUMO energy gap of 3.445 eV and an electrophilicity index of 5.8303 eV. ADMET profiling using SwissADME, ADMETlab 3.0, and ProTox 3.0 demonstrated acceptable drug-likeness parameters, favorable absorption characteristics, and low toxicity profiles. These coumarine-1,2,3-triazole hybrids represent moderate-potency antibacterial and antioxidant scaffolds warranting further structural optimization.
Therapeutic potential of sulfonate-based hydrazide hydrazones in neurodegenerative diseases: SAR insights and molecular modeling studies.
Aktar BSK, Karaküçük-İyidoğan A, Yılmaz GT … +5 more , Oruç-Emre EE, Sıcak Y, Bakırdöven A, Turgut-Solak ZD, Öztürk M
Future Med Chem · 2026 Jun · PMID 42083474 · Full text
AIMS: Cholinesterase inhibitors represent an important therapeutic strategy in combating Alzheimer's disease. MATERIAL AND METHODS: The novel 4-((2-(substitutedbenzoyl)hydrazinylidene)methyl)phenyl 2/3/4-(trifluoromethox...
AIMS: Cholinesterase inhibitors represent an important therapeutic strategy in combating Alzheimer's disease. MATERIAL AND METHODS: The novel 4-((2-(substitutedbenzoyl)hydrazinylidene)methyl)phenyl 2/3/4-(trifluoromethoxy)benzene-1-sulfonates (1-40) were synthesized from the reaction of 4-Formylphenyl-2/3/4-trifluoromethoxybenzene-1-sulfonate with various substituted benzoic acid hydrazides. The structures of all hybrid molecules were conclusively elucidated by elemental analysis and some spectroscopic techniques (IR, NMR, MS). These compounds were evaluated for their cholinesterase (AChE and BChE) inhibitory activities. RESULTS: Compound , carrying a nitro group at the 4-position of the phenyl ring among the series, exhibited the highest inhibitory activity, showing IC values of 8.11 ± 0.52 µM for AChE and 12.09 ± 0.28 µM for BChE. The molecular docking studies elucidated the interactions of the active compounds with the actives sites of AChE and BChE enzymes were elucidated by molecular docking, supporting their observed anticholinesterase activity. CONCLUSION: The compatible results of experimental data and in silico analyses demonstrate that these compounds can be considered among effective and potential lead candidates for cholinesterase inhibition targeting AD.
Quinoline-piperazine molecular hybrids as potential antimalarial agents.
Punmiya A, Vora A
Future Med Chem · 2026 Jun · PMID 42053122 · Full text
Malaria is one of the most prevalent infectious diseases worldwide, posing a significant threat in the malaria-endemic areas. The rapid emergence of strains resistant to the existing antimalarial drugs underscores the n...
Malaria is one of the most prevalent infectious diseases worldwide, posing a significant threat in the malaria-endemic areas. The rapid emergence of strains resistant to the existing antimalarial drugs underscores the necessity for discovering the next generation of antimalarial drugs with reduced resistance and enhanced potency. Quinoline-based compounds have been long recognized for their remarkable antimalarial efficacy due to their ability to interfere with heme detoxification within the parasites and have been extensively modified to generate molecules with improved pharmacological potential and overcome the resistance. Among the various strategies employed, the incorporation of piperazine moiety has gained considerable attention, as it can improve pharmacokinetic properties, molecular flexibility, and target interactions. Consequently, quinoline-piperazine hybrids have emerged as promising candidates with enhanced antimalarial potential. This review underscores recent advances in the development of quinoline-piperazine hybrids as antimalarial agents, emphasizing their activity against chloroquine-sensitive and resistant strains. In addition, structure-activity relationship () trends influencing potency, selectivity, and resistance profiles are discussed. These insights will facilitate the rational design and development of novel chemical entities as next-generation antimalarials.
Cyclization, amino acid coupling, docking-based virtual screening and SAR: showing a strategy of the structural modification for salvianic acid A.
Wu J, Zhang X, An W … +7 more , Yang Y, Zhang P, Wang Y, Zhao S, Feng Q, Zhao M, Peng S
Future Med Chem · 2026 Jun · PMID 42027185 · Full text
AIM: Providing diverse modification remains to be a strategy for salvianic acid A. MATERIALS AND METHODS: Based on the docking virtual screening, salvianic acid A was cyclized, then modified with amino acid to provide 19...
AIM: Providing diverse modification remains to be a strategy for salvianic acid A. MATERIALS AND METHODS: Based on the docking virtual screening, salvianic acid A was cyclized, then modified with amino acid to provide 19 derivatives (), and evaluated their effects on platelet aggregation, thrombus formation, and determine serum levels of P-selectin and GPIIb/IIIa in male SD rats. RESULTS: The evaluation showed that 6a-s effectively against platelet-activating factor (PAF) and adenosine diphosphate (ADP) induced platelet aggregation. The anti-arterial thrombosis assay showed that 30 nmol/kg of significantly decreased thrombus weights of rats, (3R)-6,7-dihydroxy-1,1- dimethylisochromane-3-carboxyl-Lys () possessed the strongest anti-arterial thrombotic activity. The thrombolytic assay showed that the activities of 30 nmol/kg of were significantly higher than that of saline solution (NS), had the strongest activity. The ELISA assay showed that effectively decreased the serum P-selectin and GPIIb/IIIa level. CONCLUSION: can effectively inhibited PAF and ADP induced platelet aggregation , at 30 nmol/kg dose they significantly decreased the weight of thrombus and significantly increased the potential of dissolve the clots. Specially, was particularly superior and could be a promising candidate for the afterward development. Additionally, the benefits of the 19 derivatives were associated with the serum level of P-selectin and GPIIb/IIIa.
Design, synthesis and biological evaluation of a 4,6-di(aziridin-1-yl)-1,3,5-triazine-benzimidazole hybrid as a potential dual-targeting anticancer agent.
Chernov IS, Protas AV, Popova EА … +11 more , Shemchuk OS, Petukhova NV, Babayeva G, Tretiakova VM, Bulakov VE, Kozhukhov PK, Mikolaichuk OV, Kornyakov IV, Pokrovsky VS, Semenov KN, Sharoyko VV
Future Med Chem · 2026 May · PMID 42017253 · Full text
AIMS: This study aimed to develop a novel aziridine-1,3,5-triazine derivative combining DNA-alkylating aziridine rings with a benzimidazole-containing fragment associated with PARP-related chemotypes. MATERIALS AND METHO...
AIMS: This study aimed to develop a novel aziridine-1,3,5-triazine derivative combining DNA-alkylating aziridine rings with a benzimidazole-containing fragment associated with PARP-related chemotypes. MATERIALS AND METHODS: The synthesis of target (4,6-di(aziridin-1-yl)--(2-(4-((2-methyl-1-benzo[]imidazol-1-yl)methyl)-1-1,2,3-triazol-1-yl)ethyl)-1,3,5-triazin-2-amine () was achieved through a multi-step approach, involving the synthesis of 2-methyl-1-(prop-2-yn-1-yl)-1-benzo[d]imidazole () and subsequent click chemistry reaction with -(2-azidoethyl)-4,6-di(aziridin-1-yl)-1,3,5-triazin-2-amine (). Protein modeling, docking and molecular dynamics were performed using the Schrödinger suite. Compound was evaluated for cytotoxicity (HCT-116, U87, HeLa, A549 and ECV304 cell lines) by MTT assay, genotoxicity in HCT-116 cells by DNA-comet assay, and in A549 and HCT-116 xenografts in immunodeficient BALB/c Nude mice. RESULTS: Docking/MD suggested a PARP-1 binding mode, with key interactions comparable to established inhibitors such as talazoparib and olaparib. cytotoxicity assays against HCT-116, U87, HeLa, and A549 cell lines revealed dose-dependent antiproliferative effects, with values of 14.12, 33.52, 44.60, and 26.4 µM, respectively. genotoxicity assays showed that incubation of HCT-116 cell line with the compound causes dose-dependent damage to DNA integrity. , compound inhibited tumor growth in A549 xenografts (up to 75.1%, < 0.05) and demonstrated dose-dependent activity in HCT-116 xenografts (up to 82.9% TGI at 6 mg/kg, i.v.).
Importance of five membered heterocyclic compounds in treatment of chronic myeloid leukemia by targeting various pathways.
Ninave R, Mourya A, Prajapati N
Future Med Chem · 2026 Jun · PMID 42011924 · Full text
Chronic myeloid leukemia (CML) is a clonal hematopoietic malignancy characterized by the presence of the Philadelphia chromosome, which generates the constitutively active BCR::ABL1 tyrosine kinase, driving uncontrolled...
Chronic myeloid leukemia (CML) is a clonal hematopoietic malignancy characterized by the presence of the Philadelphia chromosome, which generates the constitutively active BCR::ABL1 tyrosine kinase, driving uncontrolled myeloid proliferation. Although BCR::ABL1-targeted tyrosine kinase inhibitors (TKIs) have significantly improved CML management, challenges such as drug resistance, intolerance, and long-term adverse effects persist. To overcome these limitations, recent research has focused on developing next-generation TKIs and alternative molecular scaffolds capable of bypassing resistance mechanisms. Among these, five-membered heterocyclic compounds have gained considerable attention due to their structural diversity, favorable pharmacokinetic properties, and ability to interact with multiple biological targets. Several clinically relevant agents, including dasatinib, ponatinib, and asciminib, incorporate such heterocyclic frameworks, highlighting their therapeutic significance. In addition to direct inhibition of BCR::ABL1, these compounds can modulate key signaling pathways involved in CML progression, such as PI3K/Akt, MAPK, and JAK/STAT. This review explores the chemical diversity, molecular interactions, and therapeutic potential of five-membered heterocyclic compounds in CML. Overall, these scaffolds represent promising candidates for developing more effective and less toxic treatment strategies, improving long-term patient outcomes.
Design and synthesis of novel antibacterial hybrids combining quinoline and thiazole moieties.
Aref MMA, Al-Hussain SA, Abdel Halim AS … +4 more , Ali HI, Zaki MEA, Abdelhamed MN, Muhammad ZA
Future Med Chem · 2026 May · PMID 42007534 · Full text
AIM: The emergence of bacterial resistance underlines the urgent need for antibacterial agents with novel structures and mechanisms. We designed quinoline-thiazole hybrids by combining two privileged pharmacophores with...
AIM: The emergence of bacterial resistance underlines the urgent need for antibacterial agents with novel structures and mechanisms. We designed quinoline-thiazole hybrids by combining two privileged pharmacophores with established antibacterial properties.. METHODS: Fifteen novel derivatives were synthesized from quinoline-thiosemicarbazone precursors via reactions with phenacyl bromide and chloroacetic acid, followed by aldehyde condensation. Structures were confirmed by spectral analyses. Antibacterial activity was evaluated against MSSA, MRSA, and VRSA strains, and the most potent compounds were further assessed for antibiofilm activity, Cytotoxicity against WI38 fibroblasts (MTT assay), and potential inhibition of D-alanine-D-alanyl carrier protein ligase (SaDltA) via molecular docking. RESULTS: Nine compounds demonstrated potent activity against MSSA (MIC: 0.59-2.2 µM) and MRSA (MIC: 1.08-9.08 µM), comparable to vancomycin (0.34 and 1.35 µM, respectively). Notably, several derivatives surpassed vancomycin in antibiofilm activity against both MSSA and MRSA. Cytotoxicity assessment revealed a favorable safety profile (IC₅₀: 410.13-3246.1 µM). Molecular docking demonstrated significant DltA binding (ΔG: -13.29 to -7.75 kcal/mol), suggesting a plausible mechanism for MRSA inhibition. CONCLUSION: Quinoline-thiazole hybrids exhibited potent antibacterial and antibiofilm activities, with favorable drug-like properties, positioning them as promising candidates for the treatment of multidrug-resistant staphylococcal infections.
Molecular strategies for heterocyclic frameworks in antidiabetic drug discovery: a vision from 2020-2024.
Tahlan S, Singh S, Dey H … +2 more , Kaira M, Pandey KC
Future Med Chem · 2026 Apr · PMID 42003351 · Full text
Diabetes mellitus represents a global health crisis requiring innovative therapeutic strategies beyond traditional treatments. This comprehensive review analyzes heterocyclic frameworks developed between 2020-2024 for an...
Diabetes mellitus represents a global health crisis requiring innovative therapeutic strategies beyond traditional treatments. This comprehensive review analyzes heterocyclic frameworks developed between 2020-2024 for antidiabetic drug discovery, highlighting structure-activity relationships (SAR), molecular docking insights, and therapeutic mechanisms. Key scaffold classes emerged as potent antidiabetic agents, with benzimidazoles and triazoles demonstrating dual α-amylase/α-glucosidase inhibition (IC values 1.20-22.46 µg/mL), thiazolidinediones and quinazolines showing PPAR-γ agonism with improved insulin sensitivity and reduced cardiovascular risks, DPP-4 inhibitory scaffolds (pyrrolidines, pyrimidines) achieving IC values as low as 0.021 µM, and SGLT2-targeting heterocycles exhibiting glucose-lowering effects with cardio-renal protection. Major findings revealed that electron-donating groups (methoxy, hydroxyl) consistently enhanced binding affinity across multiple targets, halogen substitutions (fluoro, chloro, bromo) improved metabolic stability and selectivity, hybrid molecules combining multiple pharmacophores achieved superior multi-target effects, and natural product-derived heterocycles (flavonoids, coumarins, alkaloids) showed ICvalues 10-100× better than acarbose. Emerging frontiers include multi-agonist therapies (GLP-1/GIP, dual SGLT1/SGLT2 inhibitors), glucokinase activators for insulin-independent glucose control, microbiome-targeting agents, and AI-driven rational drug design integrating SAR, docking, and ADMET prediction. This review provides a strategic framework for developing safer, more selective antidiabetic agents through systematic exploitation of heterocyclic chemistry, advancing toward personalized diabetes management.
Design, synthesis, and antidiabetic activity of new furan-clubbed 1,2,3-triazole derivatives as -glucosidase inhibitors.
Devi P, Maity S, Singh A … +3 more , Mehan S, Singh G, Asati V
Future Med Chem · 2026 May · PMID 41994872 · Full text
AIM: The study aims to design, synthesize, and evaluate novel furan-clubbed 1,2,3-triazole derivatives as potential α-glucosidase inhibitors for the management of diabetes mellitus. MATERIALS AND METHODS: Ten furan-clubb...
AIM: The study aims to design, synthesize, and evaluate novel furan-clubbed 1,2,3-triazole derivatives as potential α-glucosidase inhibitors for the management of diabetes mellitus. MATERIALS AND METHODS: Ten furan-clubbed-1,2,3-triazole derivatives were synthesized and characterized through sophisticated instrumentation techniques, including FT-IR, H NMR, C NMR, and LC-MS. The compounds were assessed for their ability to inhibit the α-glucosidase enzyme. The antidiabetic effect of the best molecules was evaluated using STZ-nicotinamide induced diabetic mouse model. The observed results were further supported by molecular docking against α-glucosidase (PDB ID: 3L4U) and histopathological examinations. RESULTS: The results of studies showed that the test compound PD-10 exhibited the strongest α-glucosidase inhibition (IC = 13.82 μM), outperforming acarbose (IC = 32.03 μM), followed by and . Further, the antidiabetic evaluation of the best compounds adjudged compound as the best molecule among the series. Docking analyses indicated a significant binding affinity of (-4.34 kcal/mol). CONCLUSIONS: The research highlights as a promising α-glucosidase inhibitor with strong and antidiabetic effects, supported by favorable molecular docking interactions, and emphasizes its potential for development as an antidiabetic lead for further studies and evaluations.
Integrated computational and biological assessment of novel piperazine and piperidine-substituted 1,2,4-oxadiazoles for lung cancer therapy.
Kumar D, Jangir M, Chaurasia A
Future Med Chem · 2026 May · PMID 41989277 · Full text
AIMS: To design and synthesize a novel series of piperazine- and piperidine-substituted 1,2,4-oxadiazole derivatives and evaluate their anticancer potential, with particular interest in possible interaction with the epid...
AIMS: To design and synthesize a novel series of piperazine- and piperidine-substituted 1,2,4-oxadiazole derivatives and evaluate their anticancer potential, with particular interest in possible interaction with the epidermal growth factor receptor (EGFR). MATERIALS AND METHODS: The target compounds were synthesized using established heterocyclic strategies and characterized by standard spectroscopic techniques. Molecular docking studies were performed using the EGFR tyrosine kinase domain (PDB ID: 3OW4) to predict binding modes and ligand-receptor interactions. In vitro cytotoxic activity was assessed against A549 human lung carcinoma cells using the MTT assay. RESULTS: Docking analysis suggested favorable binding orientations within the EGFR ATP-binding site and predicted interactions with key amino acid residues. studies demonstrated dose-dependent antiproliferative activity for all compounds. Among them, compound exhibited the highest activity, with an IC value of 26.98 µM. CONCLUSIONS: The synthesized 1,2,4-oxadiazole derivatives display moderate antiproliferative activity and represent preliminary lead structures for further optimization. While molecular modeling suggests potential EGFR interaction, additional biochemical studies are required to confirm the precise mechanism of action.
Chrysin and derivatives: therapeutic potential in the patent landscape.
Silva Cezar SV, Santos AB, Dos Santos NN … +5 more , Bernardes Brasileiro M, Mendonça Santos A, Carvalho Nascimento Júnior JA, Bereau D, Serafini MR
Future Med Chem · 2026 May · PMID 41989072 · Full text
Natural compounds represent approximately 35% of the pharmaceutical market, gaining prominence in the treatment of various diseases. Among them is chrysin, a flavonoid with notable antimicrobial and immunomodulatory acti...
Natural compounds represent approximately 35% of the pharmaceutical market, gaining prominence in the treatment of various diseases. Among them is chrysin, a flavonoid with notable antimicrobial and immunomodulatory activities. However, its low aqueous solubility and chemical instability limit its therapeutic use, highlighting the need for more soluble pharmaceutical carriers or derivatives, as well as patent analysis to map technologies and therapeutic development opportunities. Therefore, this study aimed to identify and explore trends in therapeutic strategies related to the action of chrysin and its derivatives in different pathologies, as well as their potential to increase clinical efficacy through pharmaceutical technologies. A technological survey was conducted on 36 patents registered between 1999 and 2025 in different databases. The analysis revealed peaks in patent applications in 2019 and 2024, with China as the main country and universities as the primary type of applicant. The patents demonstrated that chrysin and its derivatives exhibit complex immunological and pharmacological activities, acting on multiple cellular targets and signaling pathways. These include the inhibition of enzymes and proteins, modulation of inflammatory pathways, gene regulation, and other mechanisms. This pharmacological diversity of chrysin reinforces its relevance in patent applications, proving its efficacy and enabling new applications or therapeutic combinations.
Zinc chloride-catalyzed synthesis of indole-based α-aminophosphonates with potent antimicrobial and anticancer activities: and evaluation.
Aljohani G
Future Med Chem · 2026 Jun · PMID 41988952 · Full text
AIM: This study aimed to synthesize new α-aminophosphonate derivatives based on 2-(thiophen-2-yl)-1H-indole-3-carbaldehyde and evaluate their anticancer, antimicrobial, and drug-likeness properties supported by molecular...
AIM: This study aimed to synthesize new α-aminophosphonate derivatives based on 2-(thiophen-2-yl)-1H-indole-3-carbaldehyde and evaluate their anticancer, antimicrobial, and drug-likeness properties supported by molecular docking studies. MATERIALS & METHODS: A series of α-aminophosphonates (5a-h) were synthesized using an optimized zinc chloride (ZnCl)-catalyzed reaction. The synthesized compounds were characterized by standard spectroscopic techniques. Antiproliferative activity was evaluated using MTT assays against MCF7 and HepG2 cancer cell lines. Antimicrobial activity was assessed against Gram-positive and Gram-negative bacteria and fungi. Molecular docking and ADMET analyses were also performed. RESULTS: Compounds 5b and 5e exhibited potent cytotoxic activity against MCF7 cells with IC values of 9.5 and 9.2 µM, comparable to doxorubicin (9.4 µM). All compounds demonstrated lower cytotoxicity toward HepG2 cells. Compound 5d showed the strongest antimicrobial activity with MIC values of 10-20 µg/mL, surpassing gentamicin. Molecular docking has revealed key hydrogen-bonding and π-interactions supporting dual biological activities. ADMET profiling indicated favorable drug-like properties for compounds 5a-5e. CONCLUSION: The synthesized α-aminophosphonates represent promising candidates for future development as dual anticancer and antimicrobial agents.
Novel pyrimidine-triazole conjugates for targeted inhibition of EGFR: synthesis and biological evaluation.
Maity S, Devi P, Singh A … +4 more , Saxena A, Saha B, Ali A, Asati V
Future Med Chem · 2026 May · PMID 41988910 · Full text
AIM: To design, synthesize, and evaluate novel pyrimidine-triazole derivatives as epidermal growth factor receptor (EGFR) inhibitors for anticancer activity. MATERIALS AND METHODS: Ten derivatives () were synthesized and...
AIM: To design, synthesize, and evaluate novel pyrimidine-triazole derivatives as epidermal growth factor receptor (EGFR) inhibitors for anticancer activity. MATERIALS AND METHODS: Ten derivatives () were synthesized and assessed for cytotoxicity against A549 lung cancer cell line also performed EGFR inhibition assay. Molecular docking was performed on the ATP binding pocket of EGFR (PDB: 1XKK). RESULTS: Compounds and exhibited good cytotoxic activity (IC = 0.5 and 0.7 µM) than standard drug erlotinib (IC = of 0.9 µM). Compound showed a good binding score -8.93 kcal/mol and interactions with amino acid residues THR 854, THR 790, CYS 775, and PHE856. CONCLUSIONS: The results showed SM-1F may be used as a lead compound for further development of novel EGFR inhibitors.
Molecular basis of ebselen biological activity.
Kumar M, Garg S, Berlicki Ł
Future Med Chem · 2026 Jun · PMID 41988750 · Full text
The discovery of enzyme inhibitors has sparked global efforts to develop new therapeutics. In this regard, ebselen, an organoselenium compound, has been recognized with promising broad biological and enzyme inhibition ac...
The discovery of enzyme inhibitors has sparked global efforts to develop new therapeutics. In this regard, ebselen, an organoselenium compound, has been recognized with promising broad biological and enzyme inhibition activities of thiol-containing protein,s, which modulate the redox equilibrium. The binding mode of ebselen with thiol-proteins, typically, is based on the formation of covalent Se-S bonds with cysteine residues by opening the isoselenazolone ring, i.e. cleaving the Se-N bond, and demonstrating diverse mechanism activities in numerous disease models. The thiol-protein target engagement with ebselen can have significant effects on viral replication, cellular signaling, inflammation, oxidative stress, apoptosis, cell differentiation, immune regulation, and neurodegenerative diseases and shows antimicrobial, detoxifying, and anticancer activities, suggesting wider therapeutic applications. Over its 40-year-long history, several molecular action of the ebselen inhibition mechanism have been proposed in biological systems. It has been involved in several clinical trials, demonstrating its effectiveness as a therapeutic agent aimed at preventing and treating numerous human diseases. Based on remarkable discoveries concerning ebselen, the review describes its reactivity, mechanisms of action, and activities against various molecular targets.
Recent advances in the design and development of small molecules against Lpx enzymes for mitigating infections.
Saha S, Thapliyal N, Singh M … +1 more , Ali Bhat S
Future Med Chem · 2026 Jun · PMID 41988731 · Full text
The emergence of infections caused by the gram-negative bacterium is widely recognized as a major cause of nosocomial infections and antimicrobial resistance. In gram-negative bacteria such as , Lipid A helps maintain c...
The emergence of infections caused by the gram-negative bacterium is widely recognized as a major cause of nosocomial infections and antimicrobial resistance. In gram-negative bacteria such as , Lipid A helps maintain cell membrane integrity, and targeting its biosynthesis, known as the Raetz pathway, can be a strategic approach to control these infections. The set of Lpx enzymes involved in the synthesis of Lipid A serves as a potential target for inhibiton. This review outlines strategies for the design and development of small-molecule inhibitors of enzymes that inhibit bacterial growth and mitigate infection. techniques and synthetic procedures have been employed to develop inhibitors targeting a specific enzyme. The presence of the UDP-GlcNAc group, acyl chain-binding group, five-membered ring, amide group, benzamide group, heteroatom, and fused rings is a key set of features that provides a basic scaffold for designing Lpx inhibitors. The structural characteristics of the receptor responsible for prominent ligand interactions have also been discussed, providing a foundation for the development of selective and potent inhibitors.
The antineoplastic and therapeutic effects of quinoline compounds against ehrlich ascites carcinoma in mice.
Zahran RF, Rady GM, El-Sonbati AZ
Future Med Chem · 2026 Jun · PMID 41983597 · Full text
AIM: One of the preferred scaffolds, 8-hydroxyquinoline, has been investigated synthetically by functioning at various places by several groups in pursuit of medicinally significant compounds. This research's objective i...
AIM: One of the preferred scaffolds, 8-hydroxyquinoline, has been investigated synthetically by functioning at various places by several groups in pursuit of medicinally significant compounds. This research's objective is to investigate the antineoplastic and therapeutic effects of 8-hydroxy-7-carboxaldehydequinoline against (EAC) cells. METHODS & RESULTS: One hundred mice were detached equally into five groups [(G1) negative control; (G2) 1% DMSO; (G3) Drug group; (G4) EAC group; (G5) EAC+ tested compound]. Docking study was performed, and the antitumor effect of the compound was evaluated by hematological, biochemical, antioxidant, histopathological parameters, and levels of caspase-3 and TNF-α. The docking study showed effective interaction between tested compounds and receptors of catalase, breast cancer, and caspase3. In vivo, treatment significantly restored hematological parameters, reduced liver enzymes, lipid profiles, cardiac biomarkers, urea, creatinine, malonaldehyde, and nitric oxide, while increasing total protein, superoxide dismutase, reduced glutathione, catalase, and total antioxidant capacity levels. Our findings showed that treatment with tested compound demonstrated apoptotic effect via rising in caspase3 and declining in TNF-α levels. Histopathological examination backed with our findings. CONCLUSION: With an effective safety profile, 8-hydroxy-7-carboxaldehydequinoline exhibits potential antineoplastic efficacy against EAC through apoptotic and antioxidant mechanisms.
Unveiling the potential of zingerone-1,2,3-triazole derivatives as dual anticancer and COX-2 inhibitor: design, synthesis, and biological assessments.
Alam MM, Alsenani NI, Elhenawy AA … +8 more , Hussien RA, Althagafi SH, Alqurashi EA, Elbehairi SEI, Shati AA, Alfaifi MY, Bashir SH, Nazreen S
Future Med Chem · 2026 Jun · PMID 41982177 · Full text
AIM: Cyclooxygenase-2 (COX-2) is reported to be upregulated in many cancers that promote cancer growth and angiogenesis. Therefore, inhibiting COX-2 can inhibit cancer growth and advances its treatment. In the present wo...
AIM: Cyclooxygenase-2 (COX-2) is reported to be upregulated in many cancers that promote cancer growth and angiogenesis. Therefore, inhibiting COX-2 can inhibit cancer growth and advances its treatment. In the present work, Zingerone, a reported anticancer agent, has been hybridized with 1,2,3-triazole scaffold to develop effective anticancer compounds targeting COX-2 enzyme. MATERIALS AND METHODS: Eleven zingerone-1,2,3-triazole hybrids () have been synthesized and assessed for antiproliferative activity against HepG2, MCF-7, and HCT-116 cell lines and COX-2 inhibition. Cell cycle and apoptosis studies have also been carried out for the best candidate by flow cytometry. Molecular docking and ADMET profiles were performed to inquire about drug likeness parameters. RESULTS AND DISCUSSION: Among all the zingerone hybrids, compound was found to be the most promising cytotoxic agent with IC 1.86 against HepG2 and displayed COX-2 inhibitory effect with IC 0.21 µM. The same compound also arrests cell cycle at G2/M phase and triggers late apoptosis with 95.33% in HepG2 cells. The docking study revealed strong hydrophobic interactions with key residues of the COX-2 protein. Furthermore, zingerone hybrids possess drug-likeness properties with no mutagenicity/cardiotoxicity. CONCLUSION: Zingerone hybrid ( displayed potent anticancer and COX-2 inhibitory activity, with favorable pharmacokinetics and low toxicity.
Synergistic action of JNK activation and BChE inhibition: a novel anti- glioblastoma compound with neuroprotective profile.
Lu Z, Liao Q, Duan Y … +5 more , Wang K, He S, Lyu W, Chen X, Li Q
Future Med Chem · 2026 Jun · PMID 41982148 · Full text
OBJECTIVE: This study aims to investigate whether butyrylcholinesterase (BChE) inhibitor can be used to treat glioblastoma (GBM) and exert a neuroprotective profile. METHODS: At the cellular level, the effects of on th...
OBJECTIVE: This study aims to investigate whether butyrylcholinesterase (BChE) inhibitor can be used to treat glioblastoma (GBM) and exert a neuroprotective profile. METHODS: At the cellular level, the effects of on the proliferation, invasion, and migration of GBM cells from different species were investigated. At the animal level, the safety of in normal mice, its anti-tumor effects in GBM mice, and its effects on cognition protective function were examined. RESULTS: At the cellular level, exhibited significant inhibitory effects on the proliferation, migration, and invasion of GBM cells derived from different species. At the animal level, showed low toxicity in normal mice. Moreover, it significantly inhibited GBM tumor growth, promoted tumor cell apoptosis, suppressed neuroinflammation, protected neurons, and improved the general condition and cognitive function of GBM mice. In Western blot experiments, upregulated c-jun N-terminal kinase (JNK) levels to exert an inhibitory effect on glioma. CONCLUSION: exhibits dual effects of anti-glioblastoma and cognitive improvement, by inhibiting BChE and activating the JNK signaling pathway. is a highly promising drug for the treatment of glioblastoma with neuroprotective profile.
Pyrroloquinoline quinone scaffolds: centrality in anticancer drug design.
Sen S, Karati D
Future Med Chem · 2026 May · PMID 41969172 · Full text
The Pyrroloquinoline Quinone (PQQ) is a quinone molecule that is redox active and has important health consequences for people. Several preclinical studies reveal the anticancer property of PQQ molecule by different mole...
The Pyrroloquinoline Quinone (PQQ) is a quinone molecule that is redox active and has important health consequences for people. Several preclinical studies reveal the anticancer property of PQQ molecule by different molecular pathways. but there is a lack of clinical studies evaluating this drug in oncology. Clinical investigations have only investigated PQQ as a dietary supplement, disodium salt. The known safety profile and availability of standardized formulations provide the opportunity to advance PQQ into translational research in cancer. Future initiatives will involve testing in animal tumor models, analyzing possible synergistic effects with existing medicines, improving formulations to boost absorption, and discovering biomarkers to help patient selection.
PROTACs in 2025: from the laboratory concept to clinical breakthrough.
Xu Y, Li XY, Song J … +1 more , Zhang SY
Future Med Chem · 2026 May · PMID 41940615 · Full text
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