Synthesis and anti-mycobacterial evaluation of some new isonicotinylhydrazide analogues

AbstractThe synthesis of some new 3,4-disubstituted thiazolylideneisonicotinohydrazide derivatives 3a–k, 2-substituted thiazolidinylisonicotinamide derivatives 4a–d and pyrrolylisonicotinamide derivatives 5, 6 and 7 is described. The resulted compounds are evaluated for their in vitro antitubercular activity. The minimum inhibitory concentration (MIC) of compound 3g showed comparable in vitro activity to isoniazid against Mycobacterium tuberculosis H37Ra 7131 strain in concentration 9.77μg/mL

Synthesis, antitumor screening and cell cycle analysis of novel benzothieno[3,2-<i>b</i>]pyran derivatives

<p>Three series of benzothiophene derivatives were designed and synthesized as cytotoxic agents. The compounds were subjected to <i>in vitro</i> antitumor screening at the National Cancer Institute (NCI), Bethesda, MD. The results of the single dose screening indicated that only the benzothieno[3,2-<i>b</i>]pyran series <b>3a</b>–<b>f</b> exhibited potent and broad spectrum cytotoxic activity and was subjected to five dose cytotoxic screening. The most active compound in this study was 2-amino-6-bromo-4-(4-nitrophenyl)-4<i>H</i>-[1]benzothieno[3,2-<i>b</i>]pyran-3-carbonitrile (<b>3e</b>) with MG-MID GI₅₀, TGI, and LC₅₀ values of 0.11, 7.94 and 42.66 μM, respectively. Compound <b>3e</b> exhibited broad spectrum anticancer activity against a panel of 59 cell lines. To elucidate the underlying mechanism of compound <b>3e</b> cytotoxic activity, we examined its effect on cell cycle progression and its ability to induce apoptosis using human colon adenocarcinoma cell line (HCT-116). The effect of compound <b>3e</b> on the cell cycle progression indicated that exposure of HCT-116 cells to compound <b>3e</b> for 24 and 48 h, induced a significant disruption in the cell cycle profile including time dependent decrease in cell population at G1 phase with concomitant increase in pre-G and G2/M cell population. Moreover, compound <b>3e</b> induced time dependent increase in the percentage of early and late apoptotic and necrotic cell population. In conclusion, we were able to successfully design a new series of benzothieno[3,2-<i>b</i>]pyran derivatives with potent cytotoxic activity and their mechanism of cytotoxicity was examined.</p