Synthesis of Novel Indolyl-1,2,4-triazoles as Potent and Selective Anticancer Agents

Abstract

A diverse series of 22 indolyl-1,2,4-triazole congeners (6 and 7) have been synthesized from the reaction of indole-3-carbonitrile (4) or (5) with appropriate acid hydrazides in the presence of potassium carbonate. Synthesized compounds were evaluated for their cytotoxicity against six human cancer cell lines, and some of the compounds displayed promising activity. In particular, 3-(3',4',5'-trimethoxyphenyl)-5-(N-methyl-3'-indolyl)-1,2,4-triazole (7i) and 3-(4'-piperidinyl)-5-(N-methyl-3'-indolyl)-1,2,4-triazole (7n) were the most promising and broadly active compounds against the tested cell lines. It was interesting to note that the trimethoxyphenyl analog 7i showed twofold selective cytotoxicity against PaCa2 cell line (IC(50) 0.8 μm), whereas piperidinyl analog 7n was found to be selectively cytotoxic against MCF7 cell line (IC(50) 1.6 μm). Notably, the 4-fluorophenyl derivative 7c exhibited selective cytotoxicity against PC3 cell line (IC(50) 4 μm). The structure-activity relationship study revealed that substituents including 3,4,5-trimethoxyphenyl, 3,4-dimethoxyphenyl, 4-benzyloxy-3-methoxyphenyl, 4-piperidinyl, 4-fluorophenyl and N-methylindole are beneficial for the activity of indolyl-1,2,4-triazoles (6 and 7).

Studies of <i>in vitro</i> anti-prostate cancer potential of newer 1,2,4-triazolo-1,3,4-thiadiazines with different heteroaromatics

“…Moreover, 1,2,4-triazole nucleus has been previously emerged as promising lead to develop anti-cancer scaffolds (Kaczor et al, 2013;Zhao, 2012;Kumar et al, 2011). In this study, newer 1,2,4-triazolo[3,4-b]-1,3,4-thiadiazines bearing different heteroaryls in their core structure were yielded via efficient chemical synthesis strategies.…”

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“…After completion of reaction content was neutralized with NaHCO 3 (Esterification reaction) filtered it to remove the salt, after that 0.003 mole hydrazine hydrate was added to above Ester and refluxed for 15 hours. Product was obtained by filtration and recrystallized it from ethanol to give pure compound [16][17][18][19] . As white solid (75% yield); mp = 142˚C; IR: (KBr cm (2,4 dichloro phenyl)-3-phenyl-4,5-dihydro-1H-pyrazol-1-yl]-2-(3H-indol-3-yl) amino phenyl)-3-phenyl-4,5-dihydro-1H-pyrazol-1-yl]-2-(3H -indol -3-yl …”

Microwave Assistant Synthesis, Antifungal Activity and DFT Theoretical Study of Some Novel 1,2,4-Triazole Derivatives Containing Pyridine Moiety

“…1,2,4-Triazole rings are typically planar aromatic systems, featuring an extensive chemistry [10,11]. 1,2,4-Triazole derivatives represent one of the most biologically active classes of heterocyclic compounds, and their derivatives are characterized with a broad spectrum of biological activity, including anti-cancer activity [12], antiparasitic activity [13], larvicidal activity[14], antifungal activity [15], herbicidal activity [16,17], antioxidant activity [18], cytostatic activity [19], brassinosteroid biosynthesis inhibitors [20], antimicrobial activity [21], and so on. Some compounds had been developed as commercial fungicides or herbicides (Figure 1), such as Triadimefon, Triadimenol, Flusilazole, Flupoxamand, and so on.…”