3-(5-Dimethylamino-1-naphthalenesulphonyl)-2-(3-pyridyl)thiazolidine (YHI-1) selectively inhibits human immunodeficiency virus type 1.
3-(5-Dimethylamino-1-naphthalenesulphonyl)-2-(3-pyridyl)thiazolidi ne (YHI-1), a synthetic analogue of D-cysteinolic acid isolated from sardines (Sardinops melanostictus), was found to be a specific inhibitor of human immunodeficiency virus type 1 (HIV-1) replication in various cell cultures. YHI-1 inhibited HIV-1IIIB replication with a 50% effective concentration (EC50) of 3.35, 10.23 and 4.61 microM in MT-4 cells, peripheral blood mononuclear cells and MAGI-CCR5 cells, respectively. However, no antiviral activity was observed with non-nucleoside reverse transcriptase inhibitor (NNRTI)-resistant HIV-1 strains, such as nevirapine-resistant HIV-1HE/NEV and MKC-442-resistant HIV-1IIIB-R, or with HIV-2ROD or SIVMAC. YHI-1 failed to inhibit reverse transcriptase (RT) activity in vitro with different template-primer systems. Time-of-addition experiments, the failure to inhibit NNRTI-resistant strains and the failure to show in vitro activity against RT suggest that a metabolite of YHI-1 inside the cell acts like an NNRTI. Thus, YHI-1 seems to belong to a new class of HIV-1 inhibitor and is a good candidate for further development.
Premanathan
M
M
Department of Microbiology and Immunology, Kagoshima University Dental School, Japan.
Arakaki
R
R
Ramanan
S
S
Jinno
S
S
Baba
M
M
Yamashita
S
S
Nakashima
H
H
D000818:Animals; D019380:Anti-HIV Agents / Q000494:pharmacology*; D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line; D003545:Cysteine / Q000031:analogs & derivatives / Q000494:pharmacology; D004351:Drug Resistance / Q000235:genetics; D005399:Fishes; D016655:HIV Core Protein p24 / Q000378:metabolism; D016333:HIV Protease / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D015394:Molecular Structure; D009281:Naphthalenes / Q000494:pharmacology*; D019829:Nevirapine / Q000494:pharmacology; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology; D013844:Thiazoles / Q000737:chemistry* / Q000494:pharmacology*; D053778:Thiazolidines; D014779:Virus Replication / Q000187:drug effects
D019380:Anti-HIV Agents; D000998:Antiviral Agents; D016655:HIV Core Protein p24; D009281:Naphthalenes; D018894:Reverse Transcriptase Inhibitors; D013844:Thiazoles; D053778:Thiazolidines; C117030:YHI-1; C055419:cysteinolic acid; D019829:Nevirapine; D016333:HIV Protease; D003545:Cysteine