Design, graph theoretical analysis, density functionality theories, Insilico modeling, synthesis, characterization and biological activities of novel thiazole fused quinazolinone derivatives

Abstract

Hit, Lead & Candidate Discovery A series of 2‐(2‐substituted benzylidenehydrazinyl‐2‐oxopropyl)‐3‐(4‐[4‐oxo‐2‐phenylthiazolo din‐3‐yl]phenyl)quinazolin‐4(3H)‐one 7a‐7l were synthesized and characterized by IR, 1H‐NMR, 13C‐NMR, mass spectroscopy and elemental analyses. In this present study, the density functionality theory was performed to identify drug stability. Further we introduced graph theoretical analysis by utilised Kyoto Encyclopedia of Genes and Genomes (KEGG) database and Cytoscape software to identify drug target. Based on the observed drug target insilico modeling was executed to know effective drug. The antiepileptic effects of title compounds were evaluated by using MES and subcutaneous pentylenetetrazole (scPTZ) test. Acute neurological toxicity of title compounds was studied by using standardized rotorod test. After 0.5 hr of period many of the compounds showed anticonvulsant activity at MES or scPTZ test. Comparison of the biological activity of test compounds with its chemical structures indicates that, compounds possessing electron donating group exhibited superior activity than the analogs having electron withdrawing moieties. Among the electron donating group tested, amino derivative exhibited good activity than rest of derivatives. From the study it was concluded that, the compound 7j was established as very potent compared with rest of the compounds and standard drugs subjected to biological studies. Thus the compound 2‐(2‐[4‐aminobenzylidene]hydrazinyl‐2‐oxopropyl)‐3‐(4‐[4‐oxo‐2‐phenylthiazolidin‐3‐yl]phenyl) quinazolin‐4(3H)‐one (7j) came out as pilot derivative without any neurotoxicity with a wide spectrum of antiepileptic activity. Highlights The performed work is having great significance in terms of Graph theoretical analysis used to identify drug target In silico modeling used to identify designed drug interaction with identify target Density functionality studies used to identify synthesized compound energy band gap which is correlate with enhancement of its biological activity Antiepileptic effects of entire synthesized quinazolinone scaffolds were evaluated by MES and scPTZ test 2‐(2‐[4‐aminobenzylidene]hydrazinyl‐2‐oxopropyl)‐3‐(4‐[4‐oxo‐2‐phenylthiazolidin‐3‐yl]phenyl) quinazolin‐4(3H)‐one (7j) was established as very potent compared to the rest of the compounds and standard drugs which were subjected to biological studies

Thiazolidinone‐Heterocycle Frameworks: A Concise Review of Their Pharmacological Significance

“…A series of quinazolinone containing thiazolidin‐4‐one derivatives 42 reported by Saravanan and co‐workers were screened for their anticonvulsant activity by using MES and subcutaneous pentylenetetrazole (scPTZ) test at a dose level of 30, 100, and 300 mg/kg at 0.5 hr and 4.0 hr time interval [65] . The acute toxicity studies of the screened compounds showed that they were not toxic and well‐tolerated by test animals (mice) at a 2000 mg/kg dose after oral administration.…”

Design,in silicomodelling and functionality theory of folate-receptor-targeted myricetin-loaded bovine serum albumin nanoparticle formulation for cancer treatment

“…From the optimized structure the frontier molecular orbital energies (E HOMO , E LUMO and their energy gap Eg) of Myr were derived. Using the GaussView molecular visualization programme, the obtained molecular orbital energy diagram was visualized [47].…”

Design and Synthesis of Novel 1-substituted-3-(3-(3-nitrophenyl)-4-oxo-3,4-dihydrobenzopyrimidin-2-yl amino) Isothioureas for their Anti-HIV, Antibacterial Activities, Graph Theoretical Analysis, Insilico Modeling, Prediction of Toxicity and Metabolic Studies

“…Kyoto encyclopedia of genes and genomes database was utilized for the study of graph theoretical analysis. The influential proteins was recognized and chosen by network of protein interaction (mtu: 00770) in homo sapiens [25][26][27][28].…”