Molecular docking , Synthesis and ADME Studies of New Pyrazoline Derivatives as Potential Anticancer Agents.

Abstract

Cancer is a significant worldwide public health issue. The adverse effects of anticancer chemotherapies still compromise the quality of life of patients. To identify new potential targeted anticancer agents, a series of pyrazoline derivatives were synthesized and evaluated for anticancer effects on A549 (human lung adenocarcenoma cell line). In silico evaluation methods were done before synthesis through molecular docking via genetic optimization for ligand docking (GOLD) Suite software with EGFR tyrosine kinase and exhibited significant tyrosine kinase inhibition activities compared with Erlotinb as a reference drug due to their hydrogen bonding and short contact interaction with key amino acids and these results are compatible with the experimental findings. The new derivatives were synthesized by incorporating pyrazoline pharmacophore into nabumetone moiety as a starting molecule and the chalcone derivatives as intermediate products. The compounds structure were confirmed by 1 H-NMR, some physicochemical properties and infrared spectroscopy. An in vitro assay demonstrated that the final compounds (P1, P2, P3 and P4) exerted potent to moderate cytotoxic activity in the micromolar range with an IC50 values (15.409µM, 7.24µM, 27.05µM, 22.45µM) respectively when compared with Erlotinib (IC50 =25.23µM) while (P5&P6) show weak activity. Pharmacokinetic and physicochemical properties of the final compounds predicted by using ADME evaluations. The results showed all the synthesized compounds have high oral bioavailability and good GI absorption.

Molecular modelling, Synthesis and Antiproliferative Evaluation of New Phenyldiazenyl)-Pyrazol Schiff Base Derivatives

“…Topological polar surface area (TPSA) was calculated since it is crucial in determining medication bioavailability. (22) . All synthesized compounds' results showed that TPSA is below 140.…”

Molecular modeling, synthesis, and antiproliferative evaluation of new isoxazole ring linked by Schiff bases and azo bond

“…Compounds that are passively absorbed and have a TPSA <140 Ao are consequently assumed to have a high bioavailability; otherwise, this number denotes a low bioavailability of the molecule. [ 14 ] The ADME prediction results revealed that all compounds with TPSA <140 Ao are within the range of acceptable values. Each compound had a bioavailability of 0.55, indicating that it entered the circulatory system.…”

MgO NPs catalyzed the synthesis of novel pyridin-3-yl-pyrimidin-2-yl-aminophenyl-amide derivatives and evaluation of pharmacokinetic profiles and biological activity

“…Other challenges include resistance to chemotherapeutic drugs, a lack of selectivity, and substantial side effects in cancer treatment. As a result, novel and safest anticancer drugs with a larger range of cytotoxicity to cancer cells are required (Wabdan et al, 2021).…”