Design and Synthesis of Novel Microbicidal Spermicides

Abstract

Presently, 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 STIs are insidious and diabolic, their scale and scope is large, hidden, and open-ended, the efficacy of many "solutions" is debatable and denial is a common reaction, a global urgency that cannot be overlooked. N-9 is a spermicide which 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 STDs propagation and contraception. Yet on the contrary significant efforts are in pipeline to develop safe and effective topical 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 Microbicidal Spermicides” describes our synthetic efforts towards the development of novel and potential microbicidal spermicides. This thesis consists of six chapters. Chapter 1 highlights the rapid growth population, disease and their treatment in the introductory part. Chapter 1 also reviews the status of microbicidal spermicide in current decades. This review compiles mode of action of molecule and further subdivided into chemical structures, since 2000. It covers spermicidal agents and microbicidal spermicidal agents. The reports based on formulations are devoid to include. Chapter 2 is divided into three parts: Chapter 2.1 deals with design, synthesis and evaluation of different salts of disulfide ester of carbodithioic acid (DSE-36) as spermicidal agents. Chapter 2.2 presents a new method for the synthesis of 1,3-oxathiolane-2-thiones and its applications and Chapter 2.3 include the synthesis and biology of new derivatives of DSE as spermicidal agents. Chapter 3 describes the synthesis of 3-(azol-1-yl)phenylpropanes as microbicidal spermicides for prophylactic contraception. Chapter 4 is divided into two parts: Chapter 4.1 include the synthesis and biology of 5- nitroimidazoles as possible microbicidal spermicide and Chapter 4.2 deals with potentiating metronidazole scaffold against resistant trichomonas and human sperm: design, synthesis, biology and 3D–QSAR analysis taking inspiration from the results of Chapter 4.1 Chapter 5 presents design and synthesis of 4-nitroimidazole analogues as microbicidal spermicides. Chapter 6 describes design, synthesis and biological evaluation of alkyl 1H-azole-1- carbodithioate as antifungal spermicides.