Synthesis, crystal structure and Hirshfeld surface analysis of the hydrated form of N’, N-(1,4-phenylenebis(methanylylidene) di(iso-nicotinic hydrazide)

Ingle, Kapil S.; Mohurle, Smital A.; Bairagi, Keshab M.; Shaikh, Tabrez Rafique; Venugopala, Katharigatta N.; Chandrashekharappa, Sandeep; Gonnade, Rajesh G.; Nayak, Susanta K.

doi:10.1016/j.cdc.2020.100401

Cited by 3 publications

(1 citation statement)

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“…In persistence of our interest in pharmacologically active heterocyclic compounds [40][41][42][43][44][45][46][47][48], polymorphism studies [49][50][51][52], and the discovery of anti-inflammatory agents [53][54][55][56][57][58][59], in the present investigation, we synthesized a range of 7-methoxy indolizine derivatives as indomethacin analogues (Figure 1 and Scheme 1) to evaluate their potential as antiinflammatory agents. The title compounds (5a-e) were evaluated for their pharmacological activity against the COX-2 enzyme in order to study the influence of ethyl ester at the 1and 2-positions, ethyl at the 2-position, and the diverse substituent on the benzoyl ring at the 3-positions of the indolizine core on the biological action.…”

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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Section: Introductionmentioning

confidence: 99%

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

et al. 2021

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Synthesis, characterization and larvicidal activity of novel benzylidene derivatives of fenobam and its thio analogues with crystal insight

Nefisath

Dasappa

Haripriya

et al. 2021

Journal of Molecular Structure

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4-Aryl-1,4-Dihydropyridines as Potential Enoyl-Acyl Carrier Protein Reductase Inhibitors: Antitubercular Activity and Molecular Docking Study

Venugopala

Deb

Pillay

et al. 2021

CTMC

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Background: Tuberculosis remains one of the most deadly infectious diseases worldwide due to the emergence of multi-drug resistance (MDR) and extensively drug resistance (XDR) strains of Mycobacterium tuberculosis (MTB). Materials and Methods: Herein, the screening of a total of eight symmetrical 1,4-dihydropyridine (1,4-DHP) derivatives (4a-4h) was carried out for whole-cell anti-TB activity against the susceptible H37Rv and MDR strains of MTB. Results and Discussion: Most of the compounds exhibited moderate to excellent activity against the susceptible H37Rv. Moreover, the most promising compound 4f (against H37Rv) having para-trifluoromethyl phenyl group at 4-position and bis para-methoxy benzyl ester group at 3- and 5-positions of 1,4-dihydropyridine pharmacophore, exhibited no toxicity, but demonstrated weak activity against MTB strains resistant to isoniazid and rifampicin. In light of the inhibitory profile of the title compounds, enoyl-acyl carrier protein reductase (InhA) appeared to be the appropriate molecular target. Docking study of these derivatives against InhA receptor revealed favorable binding interactions. Further, in silico predicted ADME properties of these compounds 4a-4h were found to be in the acceptable ranges including satisfactory Lipinski’s rule of five, thereby indicating their potential as drug-like molecules. Conclusion: In particular, the 1,4-DHP derivative 4f can be considered as an attractive lead molecule for further exploration and development of more potent anti-TB agents as InhA inhibitors.

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Synthesis, crystal structure and Hirshfeld surface analysis of the hydrated form of N’, N-(1,4-phenylenebis(methanylylidene) di(iso-nicotinic hydrazide)

Cited by 3 publications

References 30 publications

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

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

Synthesis, characterization and larvicidal activity of novel benzylidene derivatives of fenobam and its thio analogues with crystal insight

4-Aryl-1,4-Dihydropyridines as Potential Enoyl-Acyl Carrier Protein Reductase Inhibitors: Antitubercular Activity and Molecular Docking Study

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