Structural investigation of methyl 3-(4-fluorobenzoyl)-7-methyl-2-phenylindolizine-1-carboxylate, an inhibitory drug towards <i>Mycobacterium tuberculosis</i>

Hasija, Avantika; Bhandary, Subhrajyoti; Venugopala, Katharigatta N.; Chandrashekharappa, Sandeep; Chopra, Deepak

doi:10.1107/s2056989020003837

Cited by 6 publications

(3 citation statements)

References 25 publications

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“…However, in organic chemistry, the maximum heterocyclic compounds possess significant biological activity [ 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 ]. Recent reports suggest that indolizine is a very attractive molecule among the heterocyclic compounds and possesses two fused ring structures with carbon and nitrogen bridging atoms.…”

Section: Introductionmentioning

confidence: 99%

“…Recent reports suggest that indolizine is a very attractive molecule among the heterocyclic compounds and possesses two fused ring structures with carbon and nitrogen bridging atoms. Further, the numerous indolizine derivatives show potential biological activities [ 16 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 ], which includes antioxidant [ 42 , 43 , 44 ], antimicrobial [ 42 , 43 , 44 , 45 , 46 ], anti-inflammatory [ 47 ], anticancer [ 48 , 49 ] and antituberculosis [ 50 ] activities.…”

Section: Introductionmentioning

confidence: 99%

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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

et al. 2021

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Candida albicans, an opportunistic fungal pathogen, frequently colonizes immune-compromised patients and causes mild to severe systemic reactions. Only few antifungal drugs are currently in use for therapeutic treatment. However, evolution of a drug-resistant C. albicans fungal pathogen is of major concern in the treatment of patients, hence the clinical need for novel drug design and development. In this study, in vitro screening of novel putative pyrrolo[1,2-a]quinoline derivatives as the lead drug targets and in silico prediction of the binding potential of these lead molecules against C. albicans pathogenic proteins, such as secreted aspartic protease 3 (SAP3; 2H6T), surface protein β-glucanase (3N9K) and sterol 14-alpha demethylase (5TZ1), were carried out by molecular docking analyses. Further, biological activity-based QSAR and theoretical pharmacokinetic analysis were analyzed. Here, in vitro screening of novel analogue derivatives as drug targets against C. albicans showed inhibitory potential in the concentration of 0.4 µg for BQ-06, 07 and 08, 0.8 µg for BQ-01, 03, and 05, 1.6 µg for BQ-04 and 12.5 µg for BQ-02 in comparison to the standard antifungal drug fluconazole in the concentration of 30 µg. Further, in silico analysis of BQ-01, 03, 05 and 07 analogues docked on chimeric 2H6T, 3N9K and 5TZ1 revealed that these analogues show potential binding affinity, which is different from the therapeutic antifungal drug fluconazole. In addition, these molecules possess good drug-like properties based on the determination of conceptual Density Functional Theory (DFT)-based descriptors, QSAR and pharmacokinetics. Thus, the study offers significant insight into employing pyrrolo[1,2-a]quinoline analogues as novel antifungal agents against C. albicans that warrants further investigation.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

et al. 2021

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“…Synthetic indolizine derivatives have been shown to interact with a wide range of drug targets such as calcium channels [10], histamine receptors [11], and phospholipase A2 [12]. In addition, they have shown numerous pharmacological properties [13] such as analgesic [14], COX-2-inhibitory [15][16][17][18], anticancer [19,20], antidiabetic [21], antihistaminic [11], antileishmanic [22], antimicrobial [23], antimutagenic [24], antioxidant [25], antiviral [26], larvicidal [27,28], herbicidal [29], antitubercular [30][31][32][33][34][35][36][37], and alpha-7 nicotinic acetylcholine receptor (α-7 nAChR)- [38], N-meningitidis-, N-acetylneuraminic acid synthese (NmeNANAS)-inhibitory activities [39].…”

Section: Introductionmentioning

confidence: 99%

Crystallography, Molecular Modeling, and COX-2 Inhibition Studies on Indolizine Derivatives

et al. 2021

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The cyclooxygenase-2 (COX-2) enzyme is an important target for drug discovery and development of novel anti-inflammatory agents. Selective COX-2 inhibitors have the advantage of reduced side-effects, which result from COX-1 inhibition that is usually observed with nonselective COX inhibitors. In this study, the design and synthesis of a new series of 7-methoxy indolizines as bioisostere indomethacin analogues (5a–e) were carried out and evaluated for COX-2 enzyme inhibition. All the compounds showed activity in micromolar ranges, and the compound diethyl 3-(4-cyanobenzoyl)-7-methoxyindolizine-1,2-dicarboxylate (5a) emerged as a promising COX-2 inhibitor with an IC50 of 5.84 µM, as compared to indomethacin (IC50 = 6.84 µM). The molecular modeling study of indolizines indicated that hydrophobic interactions were the major contribution to COX-2 inhibition. The title compound diethyl 3-(4-bromobenzoyl)-7-methoxyindolizine-1,2-dicarboxylate (5c) was subjected for single-crystal X-ray studies, Hirshfeld surface analysis, and energy framework calculations. The X-ray diffraction analysis showed that the molecule (5c) crystallizes in the monoclinic crystal system with space group P 21/n with a = 12.0497(6)Å, b = 17.8324(10)Å, c = 19.6052(11)Å, α = 90.000°, β = 100.372(1)°, γ = 90.000°, and V = 4143.8(4)Å3. In addition, with the help of Crystal Explorer software program using the B3LYP/6-31G(d, p) basis set, the theoretical calculation of the interaction and graphical representation of energy value was measured in the form of the energy framework in terms of coulombic, dispersion, and total energy.

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Identification of potent indolizine derivatives against Mycobacterial tuberculosis: In vitro anti-TB properties, in silico target validation, molecular docking and dynamics studies

Venugopala,

Chandrashekharappa,

Deb

et al. 2024

International Journal of Biological Macromolecules

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Structural investigation of methyl 3-(4-fluorobenzoyl)-7-methyl-2-phenylindolizine-1-carboxylate, an inhibitory drug towards Mycobacterium tuberculosis

Cited by 6 publications

References 25 publications

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

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

Crystallography, Molecular Modeling, and COX-2 Inhibition Studies on Indolizine Derivatives

Identification of potent indolizine derivatives against Mycobacterial tuberculosis: In vitro anti-TB properties, in silico target validation, molecular docking and dynamics studies

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