Molecular Docking, ADME Studies, Synthesis, and Anti-oxidant Activity of Novel Quinazoline-4(3H)-one Derivatives

RGUHS Journal of Pharmaceutical Sciences

article

C. Geethapriya Loganathan¹  Pushpa D Poojar¹  Vijaya Kumar J² 

[1] Department of Pharmaceutical Chemistry, RR College of Pharmacy;Department of Pharmacology, RR College of Pharmacy

关键词: One pot;    Anthranilic acid;    Docking studies;    Anti-oxidant;   

DOI  :  10.26463/rjps.12_4_7

学科分类：药学、药理学、毒理学（综合）

来源: Rajiv Gandhi University of Health Sciences

【 摘 要 】

Background: Free radicals are linked to numerous human diseases. Free radicals can be neutralised by antioxidants, thereby reducing their negative effects. We sought to learn more about the antioxidant and free radical scavenging abilities of quinazoline derivatives in this study.Aim of the study : Drug discovery and development is a time-consuming, interdisciplinary and expensive process. Advances in computational procedures have empowered in silico routines, and specifically structure-based drug design technique, to accelerate new target choice for the improvement of lead compounds. Hence, the present work aimed to identify the potent quinazolinone compounds for synthesis.Methodology: The synthesis was carried out from the reaction of anthranilic acid and primary aromatic amines with Vilsmeier reagent (DMF/POCl3 ). Five derivatives which obeyed rule of five, having desired physio-chemical properties were synthesized (PDB code: 6DE4). The reaction occurred in few minutes under microwave irradiation providing good yields. The synthesized compounds were isolated, recrystallised by using suitable solvents, purified by Thin Layer Chromatography (TLC) and characterized by Fourier-transform infrared spectroscopy (FT-IR), Proton-Nuclear Magnetic Resonance (1 H NMR), and mass spectroscopy.Results: All the synthesized compounds (3a, 4a, 8b, 9b, 10b) were evaluated for their anti-oxidant activities by 2,2-diphenyl-1-picrylhydrazyl (DPPH), Hydrogen peroxide (H2 O2 ) assays. All of them showed significant anti-antioxidant activity, with 8b exhibiting the maximum activity compared to others.Conclusion: On comparison with standard ascorbic acid, quinazolinone derivatives were found to possess effective in vitro antioxidant activity. These quinazoline analogues could be considered as useful templates for further development to obtain more potent antioxidant activity.  Background: Free radicals are linked to numerous human diseases. Free radicals can be neutralised by antioxidants, thereby reducing their negative effects. We sought to learn more about the antioxidant and free radical scavenging abilities of quinazoline derivatives in this study.Aim of the study : Drug discovery and development is a time-consuming, interdisciplinary and expensive process. Advances in computational procedures have empowered in silico routines, and specifically structure-based drug design technique, to accelerate new target choice for the improvement of lead compounds. Hence, the present work aimed to identify the potent quinazolinone compounds for synthesis.Methodology: The synthesis was carried out from the reaction of anthranilic acid and primary aromatic amines with Vilsmeier reagent (DMF/POCl3 ). Five derivatives which obeyed rule of five, having desired physio-chemical properties were synthesized (PDB code: 6DE4). The reaction occurred in few minutes under microwave irradiation providing good yields. The synthesized compounds were isolated, recrystallised by using suitable solvents, purified by Thin Layer Chromatography (TLC) and characterized by Fourier-transform infrared spectroscopy (FT-IR), Proton-Nuclear Magnetic Resonance (1 H NMR), and mass spectroscopy.Results: All the synthesized compounds (3a, 4a, 8b, 9b, 10b) were evaluated for their anti-oxidant activities by 2,2-diphenyl-1-picrylhydrazyl (DPPH), Hydrogen peroxide (H2 O2 ) assays. All of them showed significant anti-antioxidant activity, with 8b exhibiting the maximum activity compared to others.Conclusion: On comparison with standard ascorbic acid, quinazolinone derivatives were found to possess effective in vitro antioxidant activity. These quinazoline analogues could be considered as useful templates for further development to obtain more potent antioxidant activity.

【 授权许可】

CC BY