Synthesis and anti-HIV activity evaluation of novel N′-arylidene-2-[1-(naphthalen-1-yl)-1H-tetrazol-5-ylthio]acetohydrazides

Abstract

A series of novel N 0 -arylidene-2-[1-(naphthalen-1-yl)-1H-tetrazol-5-ylthio] acetohydrazides was synthesized and evaluated, as nonnucleoside reverse transcriptase inhibitors (NNRTIs), for their in vitro HIV-1 and HIV-2 activity using the IIIB strain and ROD strain, respectively. The activity was monitored by the inhibition of the virusinduced cytopathic effect in the human T-lymphocyte (MT-4) cells. All of the new compounds were structurally confirmed by spectral analyses. Compounds 5q and 5r showed EC 50 of 29.62 lM (CC 50 of 169.24 ± 23.83lM) and 31.62 lM (CC 50 [ 309.06 lM), and resulting in selectivity index of 6 and [9, respectively. However, all newly synthesized derivatives were not active against HIV-2 replication.

Synthesis and anti-HIV activity evaluation of 2-(4-(naphthalen-2-yl)-1,2,3-thiadiazol-5-ylthio)-N-acetamides as novel non-nucleoside HIV-1 reverse transcriptase inhibitors

“…1), which exhibited significant anti-HIV-1 activities [12,13]. Inspired by these promising results and in continuation of our work on the search of novel NNRTIs [14,15], we thought it worthwhile to synthesize new compounds of TTAs having 4-(2-naphthoyl) moiety attached to 1,2,3-thiadiazole, with the aim to strengthen the p-p stacking interaction between the inhibitors and aromatic residues (such as Tyr188 or Tyr181) of RT and to obtain new biologically active compounds (Fig. 2).…”

Novel 1,2,3-thiadiazole derivatives as HIV-1 NNRTIs with improved potency: Synthesis and preliminary SAR studies

“…2), which exhibited significant anti-HIV-1 activities. 13 Inspired by these promising results and in continuation of our work on the research of novel NNRTIs, [13][14][15] we thought it is worthwhile to synthesize new compounds of TTAs based on the previous SAR analysis, with the aim to improve the interaction between the inhibitors and RT and to obtain new biologically active molecules.…”

1,2,3-Selenadiazole thioacetanilides: Synthesis and anti-HIV activity evaluation

“…14,15 In the STA analogues, the 1,2,3-selenadiazole ring was substituted by the triazole/tetrazole or 1,2,3-thiadiazole moiety in the corresponding lead compounds (Fig. 2); the other fragments which were considered to be necessary for conserving anti-HIV-1 activity, such as the 'S-CH 2 -CO-NH' linker and the 2-substituted anilides, 16 were left unchanged. Besides, the anilide phenyl ring was also replaced by several substituted heterocycles to further investigate the structure activity relationship (SAR) in this region.…”