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
Citation
Irum Shahzadi1 , Ameer Fawad ZahoorID1 *, Burak Tu¨ zu¨n2 , Asim Mansha1 , Muhammad Naveed Anjum3 , Azhar Rasul4 , Ali IrfanID1 , Katarzyna Kotwica-Mojzych5 , Mariusz MojzychID6 * 1 Department of Chemistry, Government College University Faisalabad, Faisalabad, Pakistan, 2 Plant and Animal Production Department, Technical Sciences Vocational School of Sivas, Sivas Cumhuriyet University, Sivas, Turkey, 3 Department of Applied Chemistry, Government College University Faisalabad, Faisalabad, Pakistan, 4 Department of Zoology, Government College University Faisalabad, Faisalabad, Pakistan, 5 Laboratory of Experimental Cytology, Medical University of Lublin, Lublin, Poland, 6 Department of Chemistry, Siedlce University of Natural Sciences and Humanities, Siedlce, PolanAbstract
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.
