TY - JOUR

T1 - Synthesis and Biological Evaluation of Some Coumarin–Triazole Conjugates as Potential Anticancer Agents

AU - Kishkentayeva, Anarkul s.

AU - Hamad, Mohammad saleh

AU - Pokrovsky, Mikhail a.

AU - Shaimerdenova, Zhanar r.

AU - Adekenova, Aigerim s.

AU - Mambeterzina, Gulnara k.

AU - Savelyev, Victor a.

AU - Pokrovsky, Andrey g.

AU - Shults, Elvira e.

N1 - This research was funded by the Ministry of Science and Education of the Republic of Kazakhstan (grant number: AP 19579011).

PY - 2025/3/31

Y1 - 2025/3/31

N2 - Despite the discovery of many chemotherapeutic drugs that prevent uncontrolled cell division processes, the development of compounds with higher anticancer efficacy and a lower level of side effects is an important task in modern pharmaceutical chemistry. Herein, a mild and convenient method for the preparation of N1-substituted 3-(1,2,3-triazolyl-methoxycarbonyl)coumarins or bis(coumarine-3-carboxylate)bis(triazole)alkandiyl by the copper(I)-catalyzed Huisgen cycloaddition reaction of readily available coumarin-3-carboxylic acid propynyl ester with azides or diazides has been presented. The synthesized compounds have been tested for their cytotoxicity on various cancer and noncancerous cell lines using the MTT assay. All new compounds were nontoxic on normal epithelial VERO cells. Two derivatives exhibited selectivity towards HPV-negative human cervical cancer cells, C33 A, with excellent activities in low concentrations (GI50 4.4–7.0 µM). In vitro mechanistic studies showed that bis(coumarine)bis(triazolylester) conjugate 3 induced time-dependent apoptosis in cervical cancer cell lines C33 A and CaSki, at the GI50 concentration, as measured by Annexin V-FITC/PI staining. The most active coumarin–triazolyl ester conjugate 2g possessed anticancer activities, as indicated by its ability to induce S/G2 phase cell cycle arrest at a low concentration and early apoptosis in CaSki cells. The obtained results revealed the potential of new compounds as anticancer agents, particularly against cervical cancer.

AB - Despite the discovery of many chemotherapeutic drugs that prevent uncontrolled cell division processes, the development of compounds with higher anticancer efficacy and a lower level of side effects is an important task in modern pharmaceutical chemistry. Herein, a mild and convenient method for the preparation of N1-substituted 3-(1,2,3-triazolyl-methoxycarbonyl)coumarins or bis(coumarine-3-carboxylate)bis(triazole)alkandiyl by the copper(I)-catalyzed Huisgen cycloaddition reaction of readily available coumarin-3-carboxylic acid propynyl ester with azides or diazides has been presented. The synthesized compounds have been tested for their cytotoxicity on various cancer and noncancerous cell lines using the MTT assay. All new compounds were nontoxic on normal epithelial VERO cells. Two derivatives exhibited selectivity towards HPV-negative human cervical cancer cells, C33 A, with excellent activities in low concentrations (GI50 4.4–7.0 µM). In vitro mechanistic studies showed that bis(coumarine)bis(triazolylester) conjugate 3 induced time-dependent apoptosis in cervical cancer cell lines C33 A and CaSki, at the GI50 concentration, as measured by Annexin V-FITC/PI staining. The most active coumarin–triazolyl ester conjugate 2g possessed anticancer activities, as indicated by its ability to induce S/G2 phase cell cycle arrest at a low concentration and early apoptosis in CaSki cells. The obtained results revealed the potential of new compounds as anticancer agents, particularly against cervical cancer.

KW - coumarin-3-carboxylic acid

KW - alkyne

KW - azides

KW - triazoles

KW - CuAAC reaction

KW - cytotoxicity

KW - anticancer agents

UR - https://www.scopus.com/record/display.uri?eid=2-s2.0-105008930349&origin=inward&txGid=bbdd119e3f885d6c607e95a001d2e3e4

U2 - 10.3390/scipharm93020016

DO - 10.3390/scipharm93020016

M3 - Article

VL - 93

JO - Scientia Pharmaceutica

JF - Scientia Pharmaceutica

SN - 2218-0532

IS - 2

M1 - 16

ER -