A unique dithiocarbamate chemistry during design & synthesis of novel sperm-immobilizing agents.
1-Substituted piperazinecarbodithioates were obtained by an unusual removal of CS2 in benzyl substituted dithiocarbamate derivatives under acid and basic conditions during design and synthesis of 1,4-(disubstituted)piperazinedicarbodithioates as double edged spermicides. A plausible mechanism for CS2 removal has been proposed. All synthesized compounds were subjected to spermicidal, antitrichomonal and antifungal activities. Twenty-one compounds irreversibly immobilized 100% sperm (MEC, 0.06-31.6 mM) while seven compounds exhibited multiple activities. Benzyl 4-(2-(piperidin-1-yl)ethyl) piperazine-1-(carbodithioate) (18) and 1-benzyl 4-(2-(piperidin-1-yl)ethyl)piperazine-1,4-bis(carbodithioate) (24) exhibited appreciable spermicidal (MEC, 0.07 and 0.06 mM), antifungal (MIC, 0.069-0.14 and >0.11 mM) and antitrichomonal (MIC, 1.38 and 0.14 mM) activities. The probable mode of action of these compounds seems to be through sulfhydryl binding which was confirmed by fluorescence labeling of sperm thiols.
Medicinal & Process Chemistry Division, CSIR-Central Drug Research Institute, Lucknow 226031, India. vlscdri1@rediffmail.com vlscdri@gmail.com.
Santosh
S
Jangir
Veenu
V
Bala
Nand
N
Lal
Lalit
L
Kumar
Amit
A
Sarswat
Lokesh
L
Kumar
Bhavana
B
Kushwaha
Pratiksha
P
Singh
Praveen Kumar
PK
Shukla
Jagdamba Prasad
JP
Maikhuri
Gopal
G
Gupta
Vishnu Lal
VL
Sharma
D000935:Antifungal Agents / Q000138:chemical synthesis / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects; D015195:Drug Design; D005456:Fluorescent Dyes / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D007778:Lactobacillus / Q000187:drug effects; D008297:Male; D008826:Microbial Sensitivity Tests; D010879:Piperazines / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D013078:Sperm Immobilizing Agents / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D013094:Spermatozoa / Q000187:drug effects / Q000378:metabolism; D013329:Structure-Activity Relationship; D013438:Sulfhydryl Compounds / Q000378:metabolism; D013859:Thiocarbamates / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D014244:Trichomonas / Q000187:drug effects
C000596983:1-benzyl 4-(2-(piperidin-1-yl)ethyl)piperazine-1,4-bis(carbodithioate); D000935:Antifungal Agents; D005456:Fluorescent Dyes; D010879:Piperazines; D013078:Sperm Immobilizing Agents; D013438:Sulfhydryl Compounds; D013859:Thiocarbamates; C000596982:benzyl 4-(2-(piperidin-1-yl)ethyl)piperazine-1-(carbodithioate)