Dataset Information

Nopol-Based Quinoline Derivatives as Antiplasmodial Agents.

ABSTRACT: Malaria remains a significant cause of morbidity and mortality in Sub-Saharan Africa and South Asia. While clinical antimalarials are efficacious when administered according to local guidelines, resistance to every class of antimalarials is a persistent problem. There is a constant need for new antimalarial therapeutics that complement parasite control strategies to combat malaria, especially in the tropics. In this work, nopol-based quinoline derivatives were investigated for their inhibitory activity against Plasmodium falciparum, one of the parasites that cause malaria. The nopyl-quinolin-8-yl amides (2-4) were moderately active against the asexual blood stage of chloroquine-sensitive strain Pf3D7 but inactive against chloroquine-resistant strains PfK1 and PfNF54. The nopyl-quinolin-4-yl amides and nopyl-quinolin-4-yl-acetates analogs were generally less active on all three strains. Interesting, the presence of a chloro substituent at C7 of the quinoline ring of amide 8 resulted in sub-micromolar EC₅₀ in the PfK1 strain. However, 8 was more than two orders of magnitude less active against Pf3D7 and PfNF54. Overall, the nopyl-quinolin-8-yl amides appear to share similar antimalarial profile (asexual blood-stage) with previously reported 8-aminoquinolines like primaquine. Future work will focus on investigating the moderately active and selective nopyl-quinolin-8-yl amides on the gametocyte or liver stages of Plasmodium falciparum and Plasmodium vivax.

SUBMITTER: Nyamwihura RJ

PROVIDER: S-EPMC7917639 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Nopol-Based Quinoline Derivatives as Antiplasmodial Agents.

Nyamwihura Rogers J RJ Zhang Huaisheng H Collins Jasmine T JT Crown Olamide O Ogungbe Ifedayo Victor IV

Molecules (Basel, Switzerland) 20210214 4

Malaria remains a significant cause of morbidity and mortality in Sub-Saharan Africa and South Asia. While clinical antimalarials are efficacious when administered according to local guidelines, resistance to every class of antimalarials is a persistent problem. There is a constant need for new antimalarial therapeutics that complement parasite control strategies to combat malaria, especially in the tropics. In this work, nopol-based quinoline derivatives were investigated for their inhibitory a ...[more]

PMID: 33673007

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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

Nopol-Based Quinoline Derivatives as Antiplasmodial Agents.

Publications

Nopol-Based Quinoline Derivatives as Antiplasmodial Agents.

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