title: Dithiocarbamate-thiourea hybrids useful as vaginal microbicides also show reverse transcriptase inhibition: design, synthesis, docking and pharmacokinetic studies.
abstract: 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.
authors.affiliation: Medicinal & Process Chemistry Division, CSIR-Central Drug Research Institute, Sector 10, Jankipuram Ext., Lucknow 226031, India; Academy of Scientific and Innovative Research (AcSIR), New Delhi 110001, India.
authors.forename: Veenu
authors.initials: V
authors.lastname: Bala
authors.affiliation: Medicinal & Process Chemistry Division, CSIR-Central Drug Research Institute, Sector 10, Jankipuram Ext., Lucknow 226031, India.
authors.forename: Santosh
authors.initials: S
authors.lastname: Jangir
authors.affiliation: Medicinal & Process Chemistry Division, CSIR-Central Drug Research Institute, Sector 10, Jankipuram Ext., Lucknow 226031, India.
authors.forename: Dhanaraju
authors.initials: D
authors.lastname: Mandalapu
authors.affiliation: Medicinal & Process Chemistry Division, CSIR-Central Drug Research Institute, Sector 10, Jankipuram Ext., Lucknow 226031, India; Academy of Scientific and Innovative Research (AcSIR), New Delhi 110001, India.
authors.forename: Sonal
authors.initials: S
authors.lastname: Gupta
authors.affiliation: Pharmacokinetics and Metabolism Division, CSIR-Central Drug Research Institute, Lucknow 226031, India; Academy of Scientific and Innovative Research (AcSIR), New Delhi 110001, India.
authors.forename: Yashpal S
authors.initials: YS
authors.lastname: Chhonker
authors.affiliation: Medicinal & Process Chemistry Division, CSIR-Central Drug Research Institute, Sector 10, Jankipuram Ext., Lucknow 226031, India.
authors.forename: Nand
authors.initials: N
authors.lastname: Lal
authors.affiliation: Endocrinology Division, CSIR-Central Drug Research Institute, Lucknow 226031, India.
authors.forename: Bhavana
authors.initials: B
authors.lastname: Kushwaha
authors.affiliation: Pharmacokinetics and Metabolism Division, CSIR-Central Drug Research Institute, Lucknow 226031, India; Academy of Scientific and Innovative Research (AcSIR), New Delhi 110001, India.
authors.forename: Hardik
authors.initials: H
authors.lastname: Chandasana
authors.affiliation: Molecular & Structural Biology Division, CSIR-Central Drug Research Institute, Lucknow 226031, India.
authors.forename: Shagun
authors.initials: S
authors.lastname: Krishna
authors.affiliation: Toxicology Division, CSIR-Central Drug Research Institute, Lucknow 226031, India.
authors.forename: Kavita
authors.initials: K
authors.lastname: Rawat
authors.affiliation: Endocrinology Division, CSIR-Central Drug Research Institute, Lucknow 226031, India.
authors.forename: Jagdamba P
authors.initials: JP
authors.lastname: Maikhuri
authors.affiliation: Pharmacokinetics and Metabolism Division, CSIR-Central Drug Research Institute, Lucknow 226031, India; Academy of Scientific and Innovative Research (AcSIR), New Delhi 110001, India.
authors.forename: Rabi S
authors.initials: RS
authors.lastname: Bhatta
authors.affiliation: Molecular & Structural Biology Division, CSIR-Central Drug Research Institute, Lucknow 226031, India.
authors.forename: Mohammad I
authors.initials: MI
authors.lastname: Siddiqi
authors.affiliation: Toxicology Division, CSIR-Central Drug Research Institute, Lucknow 226031, India.
authors.forename: Rajkamal
authors.initials: R
authors.lastname: Tripathi
authors.affiliation: Endocrinology Division, CSIR-Central Drug Research Institute, Lucknow 226031, India.
authors.forename: Gopal
authors.initials: G
authors.lastname: Gupta
authors.affiliation: Medicinal & Process Chemistry Division, CSIR-Central Drug Research Institute, Sector 10, Jankipuram Ext., Lucknow 226031, India; Academy of Scientific and Innovative Research (AcSIR), New Delhi 110001, India. Electronic address: vlscdri1@rediffmail.com.
authors.forename: Vishnu L
authors.initials: VL
authors.lastname: Sharma
mesh_terms: D000890:Anti-Infective Agents / Q000737:chemistry / Q000494:pharmacology*; D005260:Female; D006678:HIV / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D008826:Microbial Sensitivity Tests; D062105:Molecular Docking Simulation; D013859:Thiocarbamates / Q000737:chemistry / Q000494:pharmacology*; D013890:Thiourea / Q000737:chemistry / Q000494:pharmacology*; D014246:Trichomonas vaginalis / Q000187:drug effects; D014621:Vagina
chemical_list: D000890:Anti-Infective Agents; D013859:Thiocarbamates; D013890:Thiourea
keywords: Dithiocarbamate; Microbicidal; Non-nucleoside reverse transcriptase inhibitor (NNRTI); Nonoxynol-9; Spermicidal; Thiourea