ArticlePloS one2019
Computational, crystallographic studies, cytotoxicity and anti-tubercular activity of substituted 7-methoxy-indolizine analogues.
Article in PloS one, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed.
- One-pot synthesis and biological evaluation of substituted 7-chloroindolizines as antimicrobial, antioxidant, and anti-inflammatory agents.Molecular diversity · 2026Article
- Targeting InhA for Tuberculosis Therapy: A Review of Recent Advances in Enzyme Inhibition and Drug Development.Current drug targets · 2026Review
- Pyrrole-Based Enaminones as Building Blocks for the Synthesis of Indolizines and Pyrrolo[1,2-Molecules (Basel, Switzerland) · 2023Article
- Antitubercular, Cytotoxicity, and Computational Target Validation of Dihydroquinazolinone Derivatives.Antibiotics (Basel, Switzerland) · 2022Article
- Progress Report: Antimicrobial Drug Discovery in the Resistance Era.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Anti-tubercular activity and molecular docking studies of indolizine derivatives targeting mycobacterial InhA enzyme.Journal of enzyme inhibition and medicinal chemistry · 2021Article
- Article
- Crystallography, Molecular Modeling, and COX-2 Inhibition Studies on Indolizine Derivatives.Molecules (Basel, Switzerland) · 2021Article
- Investigation of Antifungal Properties of Synthetic Dimethyl-4-Bromo-1-(Substituted Benzoyl) Pyrrolo[1,2-a] Quinoline-2,3-Dicarboxylates Analogues: Molecular Docking Studies and Conceptual DFT-Based Chemical Reactivity Descriptors and Pharmacokinetics Evaluation.Molecules (Basel, Switzerland) · 2021Article
- Recent Developments in Free Energy Calculations for Drug Discovery.Frontiers in molecular biosciences · 2021Review
- Anti-Tubercular Properties of 4-Amino-5-(4-Fluoro-3- Phenoxyphenyl)-4Antibiotics (Basel, Switzerland) · 2020Article
- Crystallography, in Silico Studies, and In Vitro Antifungal Studies of 2,4,5 Trisubstituted 1,2,3-Triazole Analogues.Antibiotics (Basel, Switzerland) · 2020Article
- Cytotoxicity and Antimycobacterial Properties of Pyrrolo[1,2-Antibiotics (Basel, Switzerland) · 2020Article
- In silico Design and Synthesis of Tetrahydropyrimidinones and Tetrahydropyrimidinethiones as Potential Thymidylate Kinase Inhibitors Exerting Anti-TB Activity AgainstDrug design, development and therapy · 2020Article
- Anti-Tubercular Activity of Substituted 7-Methyl and 7-Formylindolizines and In Silico Study for Prospective Molecular Target Identification.Antibiotics (Basel, Switzerland) · 2019Article
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16 authors.
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Abstract
Indolizines are heteroaromatic compounds, and their synthetic analogues have reportedly showed promising pharmacological properties. In this study, a series of synthetic 7-methoxy-indolizine derivatives were synthesised, characterised and evaluated for in vitro whole-cell anti-tuberculosis (TB) screening against susceptible (H37Rv) and multi-drug-resistant (MDR) strains of Mycobacterium tuberculosis (MTB) using the resazurin microplate assay method. The cytotoxicity was evaluated using the MTT assay. In silico molecular-docking study was conducted for compounds 5a-j against enoyl-[acyl-carrier] protein reductase, a key enzyme of the type II fatty acid synthesis that has attracted much interest for the development of novel anti-TB compounds. Thereafter, molecular dynamic (MD) simulation was undertaken for the most active inhibitors. Compounds 5i and 5j with the methoxy functional group at the meta position of the benzoyl group, which was at the third position of the indolizine nucleus, demonstrated encouraging anti-TB activity against MDR strains of MTB at 16 μg/mL. In silico studies showed binding affinity within the range of 7.07-8.57 kcal/mol, with 5i showing the highest binding affinity. Hydrogen bonding, π-π- interactions, and electrostatic interactions were common with the active site. Most of these interactions occurred with the catalytic amino acids (Pro193, Tyr158, Phe149, and Lys165). MD simulation showed that 5j possessed the highest binding affinity toward the enzyme, according to the two calculation methods (MM/PBSA and MM/GBSA). The single-crystal X-ray studies of compounds 5c and 5d revealed that the molecular arrangements in these two structures were mostly guided by C-H···O hydrogen-bonded dimeric motifs and C-H···N hydrogen bonds, while various secondary interactions (such as π···π and C-H···F) also contributed to crystal formation. Compounds 5a, 5c, 5i, and 5j exhibited no toxicity up to 500 μg/mL. In conclusion, 5i and 5j are promising anti-TB compounds that have shown high affinity based on docking and MD simulation results.
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