Design and Synthesis of Novel Dual Action Non-detergent Spermicides and Anti-spermatogenic Agents

Abstract

Happy family, intimate relationship and healthy children are the indication of good reproductive health which ensures that every child is wanted, every birth is secure, and every person is free of sexually transmitted disease (STD) and human immunodeficiency virus (HIV). At present time, population expansion is the growing matter of concern in the world. According to United States Census Bureau, the current estimation of global population is 6.93 billion. Furthermore, the poor family planning provisions are enhancing the spread of STDs mainly HIV/AIDS, trichomoniasis, chlamydiasis, sphyilis etc. and high risk of unwanted pregnancy. Diseases like STDs are insidious and diabolic, their scale and scope is large, hidden, and open-ended, the efficacy of many "solutions" is debatable and contradiction is a common reaction, a global urgency that cannot be overlooked. N-9, the only marketed spermicide, is commonly used as a contraceptive for many decades. None of the approaches were proved to be 100% safe and effective concurrently against HIV and STIs propagation and contraception. Yet on the contrary, noteworthy efforts are in pipeline to develop safe and effective topical spermicidal microbicides. Our efforts are basically centered to develop such a spermicide which is selective, effective, non-detergent, safer, easy to use, affordable, non-irritating to vaginal tissue, and having microbicidal properties, work through a selective mode of action. So, we attempt to design, synthesize and evaluate compounds for various biological activities in vitro like spermicidal, antitrichomonas, antifungal (anticandida), and antibacterial and their safety towards HeLa and Lactobasillus using standard protocols. The thesis entitled “Design and Synthesis of Novel Dual Action non Detergent Spermicides and Anti-spermatogenic Agents” describes our synthetic efforts towards the development of novel and potential double edged spermicides. This thesis consists of six chapters. Chapter 1 highlights the use of dithiocarbamates (DTCs) as a versatile pharmacophore in Medicinal Chemistry. It covers spermicidal, microbicidal, anticancer, antitubercular and anti-HIV activities of DTCs with different mode of actions. Chapter 2 deals with design, synthesis and biological evaluation of different substituted ammonium salts of dithiocarbamic acid as dual action spermicidal agents. Chapter 3 describes the synthesis of S-(2-Thioxo-1,3-dithiolan-4-yl) -methyl dialkylcarbamothioate and S-Thiiran-2-ylmethyl dialkylcarbamothioate via intermolecular O–S rearrangement in water. Chapter 4 is divided into two parts: Chapter 4a includes the design and regioselective synthesis of dithiocarbamates containing disulfide linkage via ring opening of cyclic trithiocarbonate with amines under solvent-catalyst free condition while Chapter 4b deals with synthesis and biological evaluation of 2,2'- disulfanediylbis(3(alkylamino)propane-2,1-diyl) bis(dimethylcarbamodithioate) for prophylactic vaginal contraception taking inspiration from the results of Chapter 4a. Chapter 5 presents bis(dialkylaminethiocarbonyl)disulfides as potent double edged microbicides. Chapter 6 describes piperazine derived antispermatogenic agents as design, synthesis and their biological evaluation in vitro.