Design, synthesis, and evaluation of indole compounds as novel inhibitors targeting Gp41.
A series of indole ring containing compounds were designed based on the structure of the gp41 complex in the region of the hydrophobic pocket. These compounds were synthesized using a Suzuki Coupling reaction, and evaluated using a fluorescence binding assay and cell-cell fusion assay. The observed inhibition constant of compound 7 was 2.1microM, and the IC(50) for cell-cell fusion inhibition was 1.1microM. Assay data indicated that 7 is a promising lead compound for optimization into an effective low molecular weight fusion inhibitor.
Department of Basic Sciences, Touro University--California, 1310 Johnson Lane, Mare Island, Vallejo, CA 94592, United States. guangyan.zhou@tu.edu
Guangyan
G
Zhou
Dong
D
Wu
Evan
E
Hermel
Edina
E
Balogh
Miriam
M
Gochin
D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001565:Benzoates / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001665:Binding Sites; D002460:Cell Line; D003198:Computer Simulation; D015195:Drug Design; D015700:HIV Envelope Protein gp41 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D023581:HIV Fusion Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013816:Thermodynamics
D019380:Anti-HIV Agents; D001565:Benzoates; D015700:HIV Envelope Protein gp41; D023581:HIV Fusion Inhibitors; D007211:Indoles