Novel N-(4-thiocyanatophenyl)-1H-1,2,3-triazole-4-carboxamides exhibit selective cytotoxic activity at nanomolar doses towards human leukemic T-cells was written by Pokhodylo, Nazariy;Finiuk, Nataliya;Klyuchivska, Olha;Tupychak, Mykola A.;Matiychuk, Vasyl;Goreshnik, Evgeny;Stoika, Rostyslav. And the article was included in European Journal of Medicinal Chemistry in 2022.Product Details of 638-07-3 The following contents are mentioned in the article:
The title compounds I (R1 = Me, Pr, CH2OMe; R2 = 2-methyl-5-chlorophenyl, 3-methoxyphenyl, 4-isopropylphenyl, etc.) were synthesized via the condensation of variety of 1H-1,2,3-triazole-4-carboxylic acids II and 4-thiocyanatoaniline using CDI as amide coupling reagents. According to computer-aided calculations, all synthesized compounds are expected to have acceptable ADME profile for drug design. The antiproliferative potency of derivatives was evaluated towards different cell lines. The specific activity of four N-(4-thiocyanatophenyl)-1H-1,2,3-triazole-4-carboxamides I (R1 = Me, R2 = 4-isopropylphenyl; R1 = Me, R2 = 3,4-dimethylphenyl; R1 = Me, R2 = 2-chloro-5-methylphenyl; R1 = Pr, R2 = phenyl) (4a, 4b, 4c, 4f) was comparable to doxorubicin (GI50 = 0.65μM) at nanomolar level against Jurkat cells in the range of GI50 0.63-0.69μM. According to the results of toxicity studies of the compounds for HEK293, HaCaT, Balb/c 3T3 cells, compound I (R1 = Me, R2 = 4-isopropylphenyl) was selected for further studies as a biocompatible agent with promising anticancer activity in the NCI60 cell lines. A remarkable antiproliferative activity of compound I (R1 = Me, R2 = 4-isopropylphenyl) towards leukemia cell lines (SR, MOLT-4; CCRF-CEM; HL-60(TB); K-562; RPMI-8226) was observed and high cytotoxicity towards the CAKI-1 (kidney cancer), LOX IMVI (melanoma) and UO-31 (renal cancer) cells lines was detected. Compound I (R1 = Me, R2 = 4-isopropylphenyl) inhibits LOX IMVI cells growth at a GI50 value of 0.15μM. Compare anal. to indicate potential mechanisms of action of novel compound, as well as in silico SwissTargetPrediction and SwissSimilarity were performed. Compound I (R1 = Me, R2 = 4-isopropylphenyl) induced morphol. changes (apoptotic bodies, membrane blebbing, chromatin condensation), and DNA fragmentation in Jurkat T-cells. It reduced mitochondrial membrane potential and induced DNA damage in Jurkat cells without binding and/or intercalation to DNA mol. This study involved multiple reactions and reactants, such as Ethyl 4-chloro-3-oxobutanoate (cas: 638-07-3Product Details of 638-07-3).
Ethyl 4-chloro-3-oxobutanoate (cas: 638-07-3) belongs to organic chlorides. Organic chlorides can be used in production of: PVC, pesticides, chloromethane, teflon, insulators. Alkyl chlorides are versatile building blocks in organic chemistry. While alkyl bromides and iodides are more reactive, alkyl chlorides tend to be less expensive and more readily available.Product Details of 638-07-3
Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics