Hit optimization studies of 3-hydroxy-indolin-2-one analogs as potential anti-HIV-1 agents

被引：24

作者：

Chander, Subhash ^{[1
,3
]}

Tang, Cheng-Run ^{[2
,4
,5
]}

Penta, Ashok ^{[1
]}

Wang, Ping ^{[2
,4
,5
]}

Bhagwat, Deepak P. ^{[3
]}

Vanthuyne, Nicolas ^{[6
]}

Albalat, Muriel ^{[6
]}

Patel, Payal ^{[1
]}

Sankpal, Sanskruti ^{[1
]}

Zheng, Yong-Tang ^{[2
]}

Sankaranarayanan, Murugesan ^{[1
]}

机构：

[1] Birla Inst Technol & Sci, Dept Pharm, Med Chem Res Lab, Pilani Campus, Pilani 333031, Rajasthan, India

[2] Chinese Acad Sci, Kunming Inst Zool, Key Lab Anim Models & Human Dis Mech, Key Lab Bioact Peptides Yunnan Prov, Kunming 650223, Yunnan, Peoples R China

[3] Maharaja Agrasen Univ, Sch Pharm, Solan 174103, Himachal Prades, India

[4] Kunming Med Univ, Sch Pharmaceut Sci, Kunming 650500, Yunnan, Peoples R China

[5] Kunming Med Univ, Yunnan Key Lab Pharmacol Nat Prod, Kunming 650500, Yunnan, Peoples R China

[6] Aix Marseille Univ, CNRS, Cent Marseille, iSm2, Marseille, France

来源：

BIOORGANIC CHEMISTRY | 2018年 / 79卷

关键词：

AIDS; Reverse transcriptase; Toxicity; Virtual screening; SAR; Docking; REVERSE-TRANSCRIPTASE INHIBITORS; RESISTANCE MUTATIONS; DRUG-RESISTANCE; HIV-1; INTEGRASE; DERIVATIVES; DISCOVERY; DESIGN; RT; REPLICATION; MECHANISMS;

D O I：

10.1016/j.bioorg.2018.04.027

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

In the current study, twenty-two compounds based upon 3-hydroxy-3-(2-oxo-2-phenylethyl)indolin-2-one nucleus were designed, synthesized and in vitro evaluated for HIV-1 RT inhibition and anti-HIV-1 activity. Compounds 3d, 5c and 5e demonstrated encouraging potency against RT enzyme as well as HIV-1 in low micromolar to nanomolar concentration with good to excellent safety index. Structure activity relationship studies revealed that halogens such as bromo or chloro at 5th the position of oxindole ring remarkably enhanced the potency against RT. Moreover, methoxy or chloro groups at the ortho position of phenyl ring also significantly favored RT inhibition activity. Seven compounds (3b, 3c, 3d, 3e, 5b, 5c and 5e) with better anti-HIV-1 potency were tested against the mutant HIV-1(K103N) strain. The putative binding mode, as well as interaction patterns of the best active compound 5c with wild HIV-1 RT were studied via docking studies.

引用

页码：212 / 222

页数：11

共 43 条

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