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Cytotoxicity and Antimycobacterial Properties of Pyrrolo[1,2-a]quinoline Derivatives: Molecular Target Identification and Molecular Docking Studies.

ABSTRACT: A series of ethyl 1-(substituted benzoyl)-5-methylpyrrolo[1,2-a]quinoline-3-carboxylates 4a-f and dimethyl 1-(substituted benzoyl)-5-methylpyrrolo[1,2-a]quinoline-2,3-dicarboxylates 4g-k have been synthesized and evaluated for their anti-tubercular (TB) activities against H37Rv (American Type Culture Collection (ATCC) strain 25177) and multidrug-resistant (MDR) strains of Mycobacterium tuberculosis by resazurin microplate assay (REMA). Molecular target identification for these compounds was also carried out by a computational approach. All test compounds exhibited anti-tuberculosis (TB) activity in the range of 8-128 µg/mL against H37Rv. The test compound dimethyl-1-(4-fluorobenzoyl)-5-methylpyrrolo[1,2-a]quinoline-2,3-dicarboxylate 4j emerged as the most promising anti-TB agent against H37Rv and multidrug-resistant strains of Mycobacterium tuberculosis at 8 and 16 µg/mL, respectively. In silico evaluation of pharmacokinetic properties indicated overall drug-likeness for most of the compounds. Docking studies were also carried out to investigate the binding affinities as well as interactions of these compounds with the target proteins.

SUBMITTER: Venugopala KN

PROVIDER: S-EPMC7277568 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Cytotoxicity and Antimycobacterial Properties of Pyrrolo[1,2-a]quinoline Derivatives: Molecular Target Identification and Molecular Docking Studies.

Venugopala Katharigatta N KN Uppar Vijayakumar V Chandrashekharappa Sandeep S Abdallah Hassan H HH Pillay Melendhran M Deb Pran Kishore PK Morsy Mohamed A MA Aldhubiab Bandar E BE Attimarad Mahesh M Nair Anroop B AB Sreeharsha Nagaraja N Tratrat Christophe C Yousef Jaber Abdulmuttaleb A Venugopala Rashmi R Mailavaram Raghu Prasad RP Al-Jaidi Bilal A BA Kandeel Mahmoud M Haroun Michelyne M Padmashali Basavaraj B

Antibiotics (Basel, Switzerland) 20200507 5

A series of ethyl 1-(substituted benzoyl)-5-methylpyrrolo[1,2-a]quinoline-3-carboxylates 4a-f and dimethyl 1-(substituted benzoyl)-5-methylpyrrolo[1,2-a]quinoline-2,3-dicarboxylates 4g-k have been synthesized and evaluated for their anti-tubercular (TB) activities against H37Rv (American Type Culture Collection (ATCC) strain 25177) and multidrug-resistant (MDR) strains of Mycobacterium tuberculosis by resazurin microplate assay (REMA). Molecular t ...[more]

PMID: 32392709

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Project description:Mycobacterium tuberculosis has instigated a serious challenge toward the effective treatment of tuberculosis. The reoccurrence of the resistant strains of the disease to accessible drugs/medications has mandate for the development of more effective anti-tubercular agents with efficient activities. Time expended and costs in discovering and synthesizing new hypothetical drugs with improved biological activity have been a major challenge toward the treatment of multi-drug resistance strain M. tuberculosis (TB). Meanwhile, to solve the problem stated, a new approach i.e. QSAR which establish connection between novel drugs with a better biological against M. tuberculosis is adopted. The anti-tubercular model established in this study to forecast the biological activities of some anti-tubercular compounds selected and to design new hypothetical drugs is subjective to the molecular descriptors; AATS7s, VE2_Dzi, SpMin7-Bhe and RDF110i. The significant of the model were observed with R2 of 0.8738, R2 adj of 0.8351 Q_cvˆ2 of 0.7127 which served as criteria to substantiate the QSAR model. More also, the model significant with the QSAR external validation criterial ''(R2test) of 0.7532. Ligand-receptor interactions between quinoline derivatives and the receptor (DNA gyrase) was carried out using molecular docking technique by employing the PyRx virtual screening software and discovery studio visualizer software. Furthermore, docking study indicates that compounds 10 of the derivatives with promising biological activity have the utmost binding energy of -18.8 kcal/mol. Meanwhile, the interaction of the standard drug; isoniazid with the target enzyme was observed with the binding energy -14.6 kcal/mol which was significantly lesser than the binding energy of the ligand (compound 10). This implies that ligand 10 could be used as a structural template to design better hypothetical anti-tubercular drugs with more efficient activities. The presumption of this research aid the medicinal chemists and pharmacist to design and synthesis a novel drug candidate against the tuberculosis. Moreover, in-vitro and in-vivo test could be carried out to validate the computational results.

Dataset Information

Cytotoxicity and Antimycobacterial Properties of Pyrrolo[1,2-a]quinoline Derivatives: Molecular Target Identification and Molecular Docking Studies.

Publications

Cytotoxicity and Antimycobacterial Properties of Pyrrolo[1,2-<i>a</i>]quinoline Derivatives: Molecular Target Identification and Molecular Docking Studies.

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