Structural findings of quinolone carboxylic acids in cytotoxic, antiviral, and anti-HIV-1 integrase activity through validated comparative molecular modeling studies

Quinolone derivatives: Potential anti‐HIV agent—development and application

“…Compared with unsubstituted and monosubstituted (R 2 position) 4‐quinolones 33a–h (IC 50 : 0.410–2.300 µM) (Figure ), the bis‐substituted analogs 33i–q (IC 50 : 0.026–0.370 µM) displayed higher inhibitory activity against IN ST . In general, the derivatives 33l–q (EC 50 : 0.290–2.340 µM and IC 50 : 0.026–0.083 µM) with alkyl at N‐1 position were more potent than the unsubstituted 33k (EC 50 : 3.400 µM and IC 50 : 0.026–0.070 µM) against HIV‐1 and IN ST, suggesting the substituents at N‐1 position had great influence on the activity. Further study indicated that incorporation of acids ( 34a,b ) or amides ( 34c,d ) or aminoethylene ( 34e ) could not improve the activity, while hydroxyalkyl ( 34f,g ) was favorable to the activity (Figure ) .…”

“…In general, the derivatives 33l–q (EC 50 : 0.290–2.340 µM and IC 50 : 0.026–0.083 µM) with alkyl at N‐1 position were more potent than the unsubstituted 33k (EC 50 : 3.400 µM and IC 50 : 0.026–0.070 µM) against HIV‐1 and IN ST, suggesting the substituents at N‐1 position had great influence on the activity. Further study indicated that incorporation of acids ( 34a,b ) or amides ( 34c,d ) or aminoethylene ( 34e ) could not improve the activity, while hydroxyalkyl ( 34f,g ) was favorable to the activity (Figure ) . Esterification of hydroxyl group was detrimental to the activity .…”

“…All 4‐quinolone derivatives 36 demonstrated great potency against HIV‐1 and IN ST with EC 50 and IC 50 values of 1–52 nM and 6–15 nM, respectively. The SAR revealed that linear and branched alkyl groups at R 1 position were better than the cycloalkyl, and iso ‐butyl was optimal. Methoxy was essential for the high anti‐HIV‐1 activity as evidenced by that the anti‐HIV‐1 activity of all methoxy‐containing compounds 36h–j (IC 50 : 1 nM) was extremely high, and thus all of them warrant further investigations.…”

“…For the N ‐hydroxylethylene 4‐quinolone derivatives 35 , the introduction of fluoro at R 1 , R 2 , or R 3 position reduced the activity. Electron‐donating methoxy at R 2 position could enhance the activity, whereas electron‐withdrawing groups such as trifluoromethyl, chloro, and cyano decreased the activity . All 4‐quinolone derivatives 36 demonstrated great potency against HIV‐1 and IN ST with EC 50 and IC 50 values of 1–52 nM and 6–15 nM, respectively.…”

Novel 4‐arylaminoquinoline‐3‐carbonitriles as Inhibitors of HIV‐1 Reverse Transcriptase

“…An HIV particle, which is approximately 145 nm in diameter and contains a linear single‐stranded RNA (ssRNA) genome encoding 15 mature viral proteins . It destroys immune system leaving the victim vulnerable to opportunistic infections, being responsible for millions of deaths worldwide . Many drugs have been developed to try to inhibit the replication of HIV.…”