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

Abstract

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.

Synthesis of 1,3‐Disubtitituted Tetrahydropyrimidinium Salts and Determination of Their Biological Properties and Molecular Docking

“…The LigPrep module [30] is used for preparation of the molecules once the protein preparation module [31] has finished preparing the protein. The Glide ligand docking tool is used to interact the generated proteins and molecules with one another [32] . To analyze the effects and effects of the researched compounds on human metabolism, the Qik‐prop module of the Schrödinger program [33] was employed while doing the ADME/T analysis (absorption, metabolism, distribution, toxicity, and excretion).…”

Novel Quinazolinone Derivatives: Potential Synthetic Analogs for the Treatment of Glaucoma, Alzheimer's Disease and Diabetes Mellitus

“…First, the molecules are optimized in the gaussian software program, then the LigPrep module [54] is prepared for calculations using optimized structures. The Glide ligand docking module [55] was used to examine the interactions between the molecules and the cancer protein after preparation. Calculations were made using the OPLS4 method in all calculations.…”

Exploring theophylline-1,2,4-triazole tethered N-phenylacetamide derivatives as antimicrobial agents: unraveling mechanisms via structure-activity relationship, in vitro validation, and in silico insights

“…Due to their substantial applications across industries, including biological, agricultural, medicinal and pharmacological fields, chemists have drawn their attention to various heterocyclic scaffolds, such as piperazines (Halimehjani et al, 2022), benzoxazole, benzothiazole (Zou et al, 2023), heterocyclic sulfonamides (Apiraksattayakul et al, 2022), benzofurans (Farhat et al, 2022), benzimidazoles (Nardi et al, 2023), thiadiazoles (Janowska et al, 2020), pyarzoles (Nazeer et al, 2023), lamivudines (Henriquez-Camacho et al, 2023), ciprofloxacin-based acetanilides (Zhang et al, 2018), triazoles (Irfan et al, 2024), quinoxalines (Montana et al, 2019), and oxadiazoles (Kerru et al, 2020;Irfan et al, 2022;Irfan et al, 2023). Notably, theophylline (Shahzadi et al, 2020;Shahzadi et al, 2022a), a naturally occurring methylxanthine, has found frequent therapeutic use in treating conditions such as asthma, respiratory deficits in premature infants, and chronic pulmonary obstructive disease (COPD). It also functions as a phosphodiesterase inhibitor (Ito et al, 2002;Saharan and Nantwi, 2006).…”

“…It also functions as a phosphodiesterase inhibitor (Ito et al, 2002;Saharan and Nantwi, 2006). Acefylline (Shahzadi et al, 2022b), a derivative of theophylline with pharmacological activity, serves various purposes, including bronchodilation, heart stimulation, diuresis, smooth muscle relaxation, antimicrobial and antituberculosis properties, and antiinflammatory effects (Foppoli et al, 2007;Mangasuli et al, 2018;Gopinatha et al, 2020;Shahzadi et al, 2020;Shahzadi et al, 2022a;Montaño et al, 2022), as illustrated in Figure 1.…”