Dithiocarbamate-thiourea hybrids useful as vaginal microbicides also show reverse transcriptase inhibition: Design, synthesis, docking and pharmacokinetic studies

被引：28

作者：

Bala, Veenu ^{[1
,6
]}

Jangir, Santosh ^{[1
]}

Mandalapu, Dhanaraju ^{[1
]}

Gupta, Sonal ^{[1
,6
]}

Chhonker, Yashpal S. ^{[3
,6
]}

Lal, Nand ^{[1
]}

Kushwaha, Bhavana ^{[2
]}

Chandasana, Hardik ^{[3
,6
]}

Krishna, Shagun ^{[4
]}

Rawat, Kavita ^{[5
]}

Maikhuri, Jagdamba P. ^{[2
]}

Bhatta, Rabi S. ^{[3
,6
]}

Siddiqi, Mohammad I. ^{[4
]}

Tripathi, Rajkamal ^{[5
]}

Gupta, Gopal ^{[2
]}

Sharma, Vishnu L. ^{[1
,6
]}

机构：

[1] Cent Drug Res Inst, CSIR, Med & Proc Chem Div, Sect 10, Lucknow 226031, Uttar Pradesh, India

[2] Cent Drug Res Inst, CSIR, Div Endocrinol, Lucknow 226031, Uttar Pradesh, India

[3] Cent Drug Res Inst, CSIR, Pharmacokinet & Metab Div, Lucknow 226031, Uttar Pradesh, India

[4] Cent Drug Res Inst, CSIR, Mol & Struct Biol Div, Lucknow 226031, Uttar Pradesh, India

[5] Cent Drug Res Inst, CSIR, Div Toxicol, Lucknow 226031, Uttar Pradesh, India

[6] Acad Sci & Innovat Res AcSIR, New Delhi 110001, India

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2015年 / 25卷 / 04期

关键词：

Dithiocarbamate; Thiourea; Non-nucleoside reverse transcriptase; inhibitor (NNRTI); Spermicidal; Microbicidal; Nonoxynol-9; IN-VITRO MODEL; NONNUCLEOSIDE INHIBITORS; ANTI-HIV; POTENT; DERIVATIVES; PREVENTION;

D O I：

10.1016/j.bmcl.2014.12.062

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Prophylactic prevention is considered as the most promising strategy to tackle STI/HIV. Twenty-five dithiocarbamate-thiourea hybrids (14-38) were synthesized as woman controlled topical vaginal microbicides to counter Trichomonas vaginalis and sperm along with RT inhibition potential. The four promising compounds (18, 26, 28 and 33) were tested for safety through cytotoxic assay against human cervical cell line (HeLa) and compatibility with vaginal flora, Lactobacillus. Docking study of most promising vaginal microbicide (33) revealed that it docked in a position and orientation similar to known reverse transcriptase inhibitor Nevirapine. The preliminary in vivo pharmacokinetics of compound 33 was performed in NZ-rabbits to evaluate systemic toxicity in comparison to Nonoxynol-9. (C) 2014 Elsevier Ltd. All rights reserved.

引用

页码：881 / 886

页数：6

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