In Vitro Anti-HIV Activity And Safety Evaluation Of Five Microbicide Candidates

Objectives: To develop high efficiency, safety and cost-effective microbicides for preventing HIV and the other sexually transmitted pathogens, in vitro anti-HIV activities of 5 compounds were tested using virus-induced syncytial formation assay, the toxicities of the compounds to genital epithelium cell lines, human primary foreskin keratinocytes and to Lactobacillus debrueckii isolated from human vagina were detected. Methods: anti-HIV-1 activity was detected by syncytial formation inhibition assay, cytotoxicity was tested by MTT assay, and anti-bacterial activity was measured by microdilution method. Results: half effective concentration (EC50) and therapeutic index (TI) for anti-HIV-1 activity are 0.42 g/ml, 11,666 for PS20; 0.042mM, 216 for M36; 1.86 g/ml, 1,075 for LN, 2.6 u mol.L-1, 653 for P536, respectively. The IC50 of PS20, M36, LN and P536 on human cervical cancer cell line, ME-180 are3.15mg/ml, 2.11mmol.L-1, 4.61mmol.L-1, 2.12mg/ml, respectively, and on HeLa cells are 2mg/ml, 5.1 mmol.L-1, 4.33mmol.L-1, 3.57mg/ml, respectively, and on primary foreskin keratinocytes are 1.47mg/ml , l.16mmol.L-1 , l.16mmol.L-1 , 3.23mg/ml, respectively. The minimalinhibition concentration (MIC) of PS20, M36, LN for normal vaginal Lactobacillus debrueckii are more than 20mg/ml, and that of P536 was 4.5 mg/ml. For the compound C416, the anti-HIV activity is low, its IC50 on ME-180, HeLa cells and primary foreskin keratinocytes is 92 mol.L-1, 170 mol.L-1 and 63 mol.L-1 , respectively; C416 shows high anti-bacterial activity, its minimum inhibition concentration (MIC) on Lactobacillus debrueckii is 60 g/ml. Conclusion: PS20, M36, LN and P536 have high anti-HIV-1 activity and low cytotoxicity to genital cells, do not affect growth of vaginal Lactobacillus debrueckii. They are potential candidates for microbicides development. However, C416 is not suitable for microbicide .