New Tripentone Analogs with Antiproliferative Activity

Abstract

Tripentones represent an interesting class of compounds due to their significant cytotoxicity against different human tumor cells in the submicro-nanomolar range. New tripentone analogs, in which a pyridine moiety replaces the thiophene ring originating the fused azaindole system endowed with anticancer activity viz 8H-thieno[2,3-b]pyrrolizinones, were efficiently synthesized in four steps with fair overall yields (34–57%). All tripentone derivatives were tested in the range of 0.1–100 μM for cytotoxicity against two human tumor cell lines, HCT-116 (human colorectal carcinoma) and MCF-7 (human breast cancer). The most active derivative, with GI50 values of 4.25 µM and 20.73 µM for HCT-116 and MCF-7 cells, respectively, did not affect the viability of Caco-2 differentiated in normal intestinal-like cells, suggesting tumor cells as the main target of its cytotoxic action. The same compound was further investigated in order to study its mode of action. Results showed that it did not exert necrotic effects, while induced a clear shift of viable cells towards early apoptosis. Flow cytometric analysis demonstrated that this compound caused cell cycle alteration, inhibiting its progression in S and G2/M phases.

Anticancer Activity of Anti-Tubercular Compound(s) Designed on Pyrrolyl Benzohydrazine Scaffolds: A Repurposing Study

“…However, in the present study, to explain the action of C8 on cell cycle distributions, A549 cells were treated with 10 µM (C8) for 24 h, and the distributions of A549 cells (treated and untreated) in various stages of the cell cycle were evaluated via flow cytometry (Figure 5). Consistent with the earlier findings [51][52][53], C8 treatment led to maximum accumulation of A549 cells at the G2/M phase (39.48%); however, untreated A549 cells showed only 9.34% cells at the G2/M phase (Table 4). In addition, cell % was markedly reduced from 88.79% to 31.22% at G0/G1 phase when A549 cells were treated with C8.…”

“…Cell cycle arrest could be correlated well with the growth inhibition of cancer cells. Reports suggest that benzohydrazide derivatives stop cell progression at the G2/M phase of the cell cycle [51][52][53]. However, in the present study, to explain the action of C8 on cell cycle distributions, A549 cells were treated with 10 µM (C8) for 24 h, and the distributions of A549 cells (treated and untreated) in various stages of the cell cycle were evaluated via flow cytometry (Figure 5).…”

Cytotoxic Activity of Organotin(IV) Derivatives with Triazolopyrimidine Containing Exocyclic Oxygen Atoms

“…Cytotoxic activity of the organotin compounds against human tumor cell lines (HCT-116, HepG2 and MCF-7) and human normal cells (16-HBE and intestinal-like differentiated Caco2 cells) was determined using the MTT colorimetric assay based on the reduction of 3-(4,5-dimethyl-2-thiazolyl)bromide-2,5-diphenyl-2H-tetrazolium (MTT) to purple formazan using mitochondrial dehydrogenases of living cells, as reported [44]. This method is commonly used to illustrate inhibition of cellular proliferation.…”

New 1,2,4-Oxadiazole Nortopsentin Derivatives with Cytotoxic Activity

“…Continuing our search for new anticancer compounds [23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40], herein we report the synthesis of a new 1-methyl-3-[3-(1-methyl-1 H -indol-3-yl)-1,2,4-oxadiazol-5-yl]-1 H -pyrrolo[2,3- b ]pyridine nortopsentin analog 1 , designed on the basis of the potent activity shown by thiazole nortopsentin analogs with a 7-azaindole portion and considering the important characteristics of the 1,2,4-oxadiazole ring found in compounds with promising biological activity. The new compounds, in which the central imidazole ring of the natural lead was replaced by a 1,2,4-oxadiazole moiety, and in which a 7-azaindole portion substituted the original indole, were prescreened against the HCT-116 colon rectal carcinoma cell line and the two most active compounds were selected and further investigated in different human tumor cell lines.…”