
Docking, Synthesis and Biological Evaluation of Novel Diketoquinoline Analogues as HIV-1 Integrase Inhibitor
Author(s) -
Kishore D. Deo,
I.J. Singhvi,
Sandeep R. Patil,
Avinash Patil
Publication year - 2019
Publication title -
asian journal of chemistry/asian journal of chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.145
H-Index - 34
eISSN - 0975-427X
pISSN - 0970-7077
DOI - 10.14233/ajchem.2019.22045
Subject(s) - raltegravir , chemistry , integrase , integrase inhibitor , nevirapine , ec50 , docking (animal) , stereochemistry , in vitro , human immunodeficiency virus (hiv) , combinatorial chemistry , biochemistry , virology , antiretroviral therapy , viral load , medicine , nursing , gene , biology
A series of novel diketoquinoline acid derivatives as potential anti-HIV-1 Integrase inhibitors were docked, synthesized and characterized by IR, NMR , CHN and MS spectral analysis. Many compounds were identified and docked in integrase pocket. The target diketoquinolines were prepared from substituted oxoquinoline-3-carboxylate. In vitro biological evaluation revealed that some of the titled compounds exhibited moderate to good anti-HIV-1 Integrase inhibitory activity in comparison with the reference drugs i.e. raltegravir and nevirapine. The cytotoxicity of most of testing compounds on C8166 were very low, the CC50 value of them were higher than 200 μM, except the few compounds. Compounds 1-5 showed weak anti-HIV-1 activity, its therapeutic index was 457, 531, 583, 869 and 909 respectively. As a positive control drug, Nevirapine has the best anti-HIV-1 activity (EC50 = 0.015-0.016 μM) in vitro and the CC50 of was higher than 200 μM, its therapeutic index was higher 12418.50. In integrase assay compound 6 and 7 showed EC50 value 0.08 μM as compared with standard drug raltegravir.