2. DEVELOPMENT OF MULTIFUNCTIONAL ANTI-HIV-1 AGENTS AS MICROBICIDES

Intensive efforts are underway worldwide to develop chemotherapeutic agents effective against the human immunodeficiency (HIV), the etiologic agent of the acquired immunodeficiency syndrome (AIDS). It is estimated that 42 million people are living with HIV/AIDS today. Women face a greater risk of acquiring HIV and are 4-17 times more likely to contract HIV, due to economic, social, and biological factors. Therefore, there is an urgent need to develop a safe over-the-counter intravaginal/intrarectal microbicide for prevention of HIV transmission in females. The purpose of this project was to develop multifunctional anti-HIV-1 microbicides by combining agents having different mechanisms of action. This aspect of my research is carried out with collaboration with Gustavo F. Doncel (EVMS, CONRAD) and Dr. Chandravanu Dash (Vanderbilt-Meharry Center for AIDS Research). 

1. Dash, C., Ahmadibeni, Y., Hanley, M. J., Pandhare, J., Gotte, M., Le Grice, S. F. J., Parang, K. Inhibition of multi-drug resistant HIV-1 reverse transcriptase by nucleoside beta-triphosphates. Bioorg. Med. Chem. Lett. (2011) doi:10:1016/j.bmcl.2011.05.005.

2. Agarwal, H. K., Doncel, G. F., Parang K. Synthesis and anti-HIV activities of Suramin conjugates of 3'-fluoro-2',3'-dideoxythymidine and 3'-azido-2',3'-dideoxythymidine. Med. Chem. In press.

3. Agarwal, H. K., Loethan, K., Mandal, D., Doncel, G. F., Parang, K. Synthesis and anti-HIV activities of fatty acyl ester derivatives of 2',3'-didehydro-2',3'-dideoxythymidine. Bioorg. Med. Chem. Lett. (2011) 21, 1917-1921.

4. Ahmadibeni, Y., Tiwari, R., Swepson, C., Pandhare, J., Dash, C., Doncel, G. F., Parang, K. Synthesis and anti-HIV activities of bis-(cycloSaligenyl) pronucleotides derivatives of 3'-fluoro-3'-deoxythymidine and 3'-azido-3'-deoxythymidine. Tetrahedron Lett. (2011) 52, 802-805.

5. Agarwal, H. K., Kumar, A., Doncel, G. F., Parang K. Synthesis, antiviral and contraceptive activities of nucleoside-sodium cellulose sulfate acetate and succinate conjugates. Bioorg. Med. Chem. Lett. (2010) 20, 6993-6997.

6. Ahmadibeni, Y., Dash, C., Le Grice, S. F. J., Parang K. Solid-phase synthesis of 5'-O-beta,gamma-methylenetriphosphate derivatives of nucleosides and evaluation of their inhibitory activity against HIV-1 reverse transcriptase. Tetrahedron Lett. (2010) 51, 3010-3013.

7. Ahmadibeni, Y., Dash, C., Hanley, M. J., Le Grice, S. F. J., Agarwal, H. K., Parang K. Synthesis of nucleoside 5'-O-alpha,beta-methylene-beta-triphosphates and evaluation of their potency towards inhibition of HIV-1 reverse transcriptase. Org. Biomol. Chem. (2010) 8, 1271-1274.

8. Agarwal, H. K., Doncel, G., Parang, K. Synthesis and anti-HIV activities of phosphate triester derivatives of 3'-fluoro-2',3'-dideoxythymidine and 3'-azido-2',3'-dideoxythymidine. Tetrahedron Lett. (2008) 49, 4905-4907.