Repositioning of acefylline as anti-cancer drug: Synthesis, anticancer and computational studies of azomethines derived from acefylline tethered 4-amino-3-mercapto-1,2,4-triazole

被引:42
作者
Shahzadi, Irum [1 ]
Zahoor, Ameer Fawad [1 ]
Tuzun, Burak [2 ]
Mansha, Asim [1 ]
Anjum, Muhammad Naveed [3 ]
Rasul, Azhar [4 ]
Irfan, Ali [1 ]
Kotwica-Mojzych, Katarzyna [5 ]
Mojzych, Mariusz [6 ]
机构
[1] Govt Coll Univ Faisalabad, Dept Chem, Faisalabad, Pakistan
[2] Sivas Cumhuriyet Univ, Tech Sci Vocat Sch Sivas, Plant & Anim Prod Dept, Sivas, Turkey
[3] Govt Coll Univ Faisalabad, Dept Appl Chem, Faisalabad, Pakistan
[4] Govt Coll Univ Faisalabad, Dept Zool, Faisalabad, Pakistan
[5] Med Univ Lublin, Lab Expt Cytol, Lublin, Poland
[6] Siedlce Univ Nat Sci & Humanities, Dept Chem, Siedlce, Poland
来源
PLOS ONE | 2022年 / 17卷 / 12期
关键词
SCHIFF-BASES; BIOLOGICAL EVALUATION; THEOPHYLLINE; DERIVATIVES; HYDRAZONES; ACID; SOLUBILITY; INHIBITOR; HYDRAZIDE; BINDING;
D O I
10.1371/journal.pone.0278027
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Novel azomethines derived from acefylline tethered triazole hybrids (7a-k) have been synthesized and evaluated against human liver cancer cell line (Hep G2) using MTT assay. The synthesized series of azomethines exhibited promising efficacy against liver cancer cell line. Screening of the synthesized series identified compound 7d with the least cell viability value (11.71 +/- 0.39%) as the most potent anticancer agent in contrast to the reference drug acefylline (cell viability = 80 +/- 3.87%). In this study, the potentials of the novel agents (7a-k) to inhibit liver cancer proteins were assessed. Subsequently, the structure-activity relationship of the potential drug candidates was assessed via ADME/T molecular screening. The cytotoxic potential of these derivatives was also investigated by hemolysis and thrombolysis. Their hemolytic and thrombolytic studies showed that all of these drugs had very low cytotoxicity and moderate clot lysis activity. Compound 7g (0.26% hemolysis) and 7k (52.1% clot lysis) were the least toxic and moderate thrombolytic agents respectively.
引用
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页数:19
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