Selected 5-amino-1-aryl-1H-1,2,3-triazole scaffolds as promising antiproliferative agents

Abstract

Development of new effective drugs with low side effects and definite chemical characteristics needs identification of bioactive scaffolds for further structural optimization. New synthesized derivatives of 4-hetaryl-5-amino-1-aryl-1H-1,2,3-triazoles and 3H-[1,2,3]triazolo[4,5-b]pyridines were tested for anticancer activity using 60 human tumor cell lines within 9 cancer types. The selective influence of (5-amino-1H-1,2,3-triazol-4-yl)quinazolin-4(3H)-ones: 2-(5-amino-1-(4-chlorophenyl)-1H-1,2,3-triazol-4-yl)quinazolin-4(3H)-one and 2-(5-amino-1-phenyl-1H-1,2,3-triazol-4-yl)-6-bromoquinazolin-4(3H)-one on ovarian cancer OVCAR-4 cells with growth percentage (GP) =-4.08 and 6.63%, respectively, was found. The derivative 5,7-diamino-3-(3-(trifluoromethyl)phenyl)-3H-[1,2,3]triazolo[4,5-b]pyridine-6-carbonitrile possessed high activity towards lung cancer EKVX cells (GP = 29.14%). The compounds were shown to be less toxic than doxorubicin towards non-tumor human embryonic kidney cells of HEK293 line. Thus, the results of our study confirm the anticancer potential of compounds based on 5-amino-1-aryl-1H-1,2,3-triazoles scaffolds and their fused polycyclic derivatives.

Synthesis, crystal structure and Hirshfeld surface analysis of 5-cyclopropyl-N-(2-hydroxyethyl)-1-(4-methylphenyl)-1H-1,2,3-triazole-4-carboxamide

“…In our previous studies, new active compounds with a 1,2,3triazolyl-4-carboxamide motif were reported (Shyyka et al, 2019;Pokhodylo, Shyyka, Finiuk & Stoika, 2020;Pokhodylo, Slyvka & Pavlyuk, 2020). Additionally, 1,2,3-triazolyl-4carboxamide derivatives were found to be inhibitors of the Wnt/-catenin signalling pathway (Obianom et al, 2019).…”

1,2,3‐Triazole hybrids as anticancer agents: A review

“…[86] 5-Amino-1H-1,2,3-triazol-4-yl)quinazolin- such as thiazole and oxadiazole led to decreased activity. [87] Maleimide-linked 1,2,3-triazole hybrid 93 showed high cytotoxicity,…”

Evaluation of the antiproliferative activity of selected 1,2,3-triazole-4-carboxylic acids — key fragments and precursors of antitumor 1,2,3-triazole-4-carboxamides

“…The ethyl 1-phenyl-5-(pyridin-3-yl)-1H-1,2,3-triazole-4-carboxylate, which inhibited the growth of these cells by 30 % (GP = 70.94 %), demonstrated similar growth value. In general, this NCI-H522 cell line was the most sensitive to such molecular scaffolds (10)(11)(12)(13)(14)17) and the average growth was 75.52 %, the percent of growth was from 68.09 to 86.18 %. Noteworthy, several compounds 10-13, 17 inhibited the thiazol-2-yl)-1H-1,2,3-triazole-4-carboxylic acid 24 showed a significant inhibitory effect on the LOX IMVI (Melanoma) cells (GP = = 44.78 % and 62.25 %, respectively).…”

“…In our previous work, we found 5-amino-1H-1,2,3-triazole-4-carboxamides as potent antiproliferative agents toward the CNS cancer SNB-75 cell line [8]. The related condensed [1,2,3] triazolo [1,5-a]pyrimidines were also studied and the compounds with cytotoxic activity were found [9,10]. The 5-(trifluo romethyl)-1H-1,2,3-triazole-4-carboxamides were discovered as c-Met-targeting and apoptosis-inducing agents for various tumour cell lines (MCF-7, HepG2, A549, H460, HT-29, MKN-45 and U87MG) with a 3-5-fold higher activity than the positive control drug foretinib [11,12].…”