Click Chemistry-Based Synthesis of Novel 1,2,3-Triazole Derivatives and Cytotoxic Activity on Breast and Prostate Cancer Cell Lines http://www.doi.org/10.26538/tjnpr/v7i7.6
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Abstract
Breast and prostate cancers are a major cause of death each year. Most available anticancer drugs are not very effective and can cause side effects. Identifying a safe and effective alternative drug with fewer side effects for long-term anticancer therapy is therefore necessary. The present study was aimed at synthesizing 1,2,3-triazole derivatives and evaluating their activity against human breast cancer (MCF-7) and prostate cancer (PC-3) cell lines. Novel series of three 1,2,3-triazole derivatives (T1, T2, and T3 compounds) were synthesized. The compounds were produced by the Cu(I)-catalyzed Huisgen 1,3-dipolar cycloaddition process. They were subsequently subjected to IR, H-NMR, and ESI-MS spectroscopic analyses. An in vitro cytotoxicity assay was conducted on each newly synthesized compound against MCF-7 and PC- 3 cells. The results showed that most of the T1, T2, and T3 test compounds exhibited significant cytotoxic action. The principal derivatives T1 and T2 are the compounds with the most promising cytotoxic activity. Furthermore, when compared to the standard 5-FU drug, the IC50 values for the compounds T1, T2, and T3 against the PC-3 cell line were 273.947, 406.303, and 314.368 M, respectively, while they were 91.476, 132.658, and 116.232 against breast cancer cells when compared to the standard drug adriamycin. The findings of this study demonstrated that the novel synthesized compounds could be used as potential anticancer drugs.
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Sangthong S, Krusong K, Ngamrojanavanich N, Vilaivan T, Puthong S, Chandchawan S, Muangsin N. Synthesis of rotenoid derivatives with cytotoxic and topoisomerase II inhibitor activities. Bioorg. Med. Chem. Lett. 2011; 21:4813-4818.
Popiolek L, Biernasiuk A, Paruch K, Malm A, Wujec M. Synthesis and in vitro antimicrobial activity screening of new pipemidic acid derivatives. Arch. Pharm. Res. 2018; 41:633-645.
Almashal FA, Khalaf M. 1,3-dipolar cycloaddition for 4- azidobenzene sulfonamide with acetylenic and olefinic compounds. Basrah J Sci. 2014; 32(1):49-69.
Kapro B, Luszczki JJ, Plazi-Nnska A, Siwek A, Karcz T, Gribo A, Nowak G, Makuch-Kocka A, Walczak K, Langner E. Development of 1,2,3-triazole-based anticonvulsant drug candidates acting on the voltage-gated sodium channels. Insights from in-vivo, in-vitro, and in-silico studies. Eur. J. Pharm. Sci. 2019; 129:42-57.
Xu Z, Zhao SJ, Liu Y. 1,2,3-triazole-containing hybrids as potential anticancer agents: Current developments, action mechanisms, and structure-activity relationships. Eur. J. Med. Chem. 2019; 183:111700-111713.
Aouad MR, Mayaba MM, Naqvi A, Bardaweel SK, Alblewi FF, Messali M, Rezki N. Design, synthesis, in silico and in vitro antimicrobial screenings of novel 1,2,4-triazoles carrying 1,2,3-triazole scaffold with lipophilic side chain tether. Chem. Cent. J. 2017; 11:117-123.
Kumar KA, Kalluraya B, Kumar SM. Synthesis and in-vitro antioxidant activities of some coumarin derivatives containing 1,2,3-triazole ring. Phosp Sulf Relat. Elem. 2018; 193:294-299.
Timur I, Kocyigit ÜM, Dastan T, Sandal S, Ceribasi AO, Taslimi P, Gulcin I, Koparir M, Karatepe M, Çiftçi MJ. In vitro cytotoxic and in vivo antitumoral of some aminomethyl derivatives of 2,4-dihydro-3H-1,2,4-triazole- 3-thiones-Evaluation of their acetylcholinesterase and carbonic anhydrase enzymes inhibition profiles. Biochem. Mol. Toxicol. 2019; 33:22239-22250.
Savanur HM, Naik KN, Ganapathi SM, Kim KM, Kalkhambkar RG. Click chemistry inspired design, synthesis, and molecular docking studies of coumarin, and quinolinone linked 1,2,3-triazoles as promising antimicrobial agents. Chem. Select. 2019; 3:5296-5303.
Rajavelu K, Subaraja M, Rajakumar P. Synthesis, optical properties, and antioxidant and anticancer activity of benzoheterazole dendrimers with triazole bridging unit. New J Chem. 2018; 42:3282-3292.
Santosh R, Selvam MK, Kanekar SU, Nagaraja GK. Synthesis, characterization, antibacterial and antioxidant studies of some heterocyclic from triazolelinked chalcone derivatives. Chem. Select. 2018; 3:6338-6343.
Golas PL, Matyjaszewski K. Click chemistry and ATRP: A beneficial union for the preparation of functional materials. QSAR Comb. Sci. 2007; 26:1116-1134.
Gierlich J, Burley GA, Gramlich PME, Hammond DM, Carell T. Click chemistry as a reliable method for the highdensity postsynthetic functionalization of alkyne-modified DNA. Org Lett. 2006; 8: 3639-3642.
Nuzziz A, Massi A, Dondoni A. Model studies toward the synthesis of thymidine oligonucleotides with triazole internucleosidic linkages via iterative Cu(I)-promoted azide-alkyne ligation. QSAR Comb Sci. 2007; 26: 1191- 1199.
El Malah T, Nour HF, Satti AAE, Hemdan BA, El-Sayed WA. Design, synthesis, and antimicrobial activities of 1,2,3-triazole glycoside clickamers. Molec. 2020; 25: 790.
Kollaschinski M, Sobotta J, Schalk A, Frischmuth T, Graf B, Serdjukow S. Efficient DNA click reaction replaces enzymatic ligation. Bioconj Chem. 2020; 31: 507-512.
Savaş B, Öztürk T, Meyvaci E, Hazer B. Synthesis and characterization of comb-type graft copolymers by redox polymerization and “click” chemistry method. SN Appl Sci. 2020; 2:18-26.
Castillo JC, Bravo NF, Tamayo LV, Mestizo PD, Hurtado T, Macias M, Portilla J. Water-compatible synthesis of 1,2,3-triazoles under ultrasonic conditions by a Cu(I) complex-mediated click reaction. ACS Omega. 2020; 5:30148-30159.
Pramod SP, Rajubai DB, Ravibhushan SK, Sambhaji TD, Prashant PD, Vagolu SK, Dharmarajan S, Vijay MK, Kishan PH. Design and synthesis of new indanol-1,2,3- triazole derivatives as potent antitubercular and antimicrobial agents. J Pre-proofs. 2020.
Al-Hujaj HH, Hassan QMA, Almashal FA, Sultan HA, Dhumad AM, Jassem AM, Emshary CA. Benzenesulfonamide-thiazole system bearing an azide group: Synthesis and evaluation of its optical nonlinear responses. Optik Int J Light Elect. 2022; 265: 169477.
Almashal FA, Al-hujaj HH, Ramadhan UH. Synthesis, characterization and biological study of two azide and two bis 1,2,3-triazole acyclonucleoside anaglues of thimen. Basrah J Sci. 2015; 44(1):84-100.
Mohammed MK, Al-Shuhaib Z, Al-Shawi AAA. Synthesis, characterization and cytotoxicity appraisal of original 1,2,3- Triazole derivatives, against breast cancer cell line (MIDAMB-231). Med J Chem. 2019; 9(4):305-310.
Ali AA, Gogoi D, Chaliha AK, Buragohain AK, Trivadi T, Saikia PJ, Gehlot PS, Kumar A, Chaturvedi V, Sarma D. Synthesis and biological evaluation of novel 1,2,3-triazole derivatives as anti-tubercular agents. Bioorg Med Chem Lett. 2017; 27:3698-3703.
Almashal FAK, Al-Hujaj HH, Jassem AM, Al-Masoudi NA. A click synthesis, molecular docking, cytotoxicity on breast cancer (MDA-MB 231) and anti-HIV activities of new 1,4-disubstituted-1,2,4-triazole thymine derivatives. Russ J Bioorg Chem. 2020; 46: 360
Ibraheem TK, Abdul Razak WAR, Shneshil MK. Synthesis of 1,2,3-triazole derivatives from azidoacetamide via cycloaddition reaction. J Pharm Sci Res. 2019; 11:540-544.
Almashal FA, Al-hujaj HH, Ramadhan UH. Synthesis, characterization and biological study of two azide and two bis 1,2,3-triazole acyclonucleoside anaglues of thimen. Basrah J Sci. 2015; 33:84-100.
Tanimoto H, Kakiuchi K. Recent applications and developments of organic azides in total synthesis of natural products. Natur Prod Comm. 2013; 8:1021-1034.
Phatak PS, Bakale RD, Kulkarni RS, Dhumal ST, Dixit PP, Krishna VS, Sriram D, Khedkar VM, Haval KP. Design and synthesis of new indanol-1,2,3-triazole derivatives as potent antitubercular and antimicrobial agents. Bioorg Med Chem Lett. 2020; 30: 127579.
Worrell BT, Malik JA, Fokin VV. Direct evidence of a dinuclear copper intermediate in Cu(I)-catalyzed azidealkyne cycloadditions. Sci. 2013; 340-457.
Ihmaid SK, Alraqa SY, Aouad MR, Aljuhani A, Elbadawy HM, Salama SA, Rezki N, Ahmad EA. Design of molecular hybrids of phthalimide-triazole agents with potent selective MCF-7 /HepG2 cytotoxicity: Synthesis, EGFR inhibitory effect, and metabolic stability. Bioorg. Chem. 2021; 111: 104835.
Madasu C, Shailaja K, Sangaraju R, Sistla R, Uppuluri VM. Synthesis and biological evaluation of some novel 1,2,3- triazole hybrids of myrrhanone B isolated from Commiphora mukul gem resin: Identification of potent antiproliferative leads active against prostate cancer cells (PC-3). Eur J Med Chem. 2019; 188: 111974.