title: Synthesis, anticonvulsant activity and molecular modeling study of some new hydrazinecarbothioamide, benzenesulfonohydrazide, and phenacylacetohydrazide analogues of 4(3H)-quinazolinone.
abstract: A new series of quinazoline analogues was designed and synthesized to get the target compounds 18-21, 30-41, 46-53, and 57-76. The Obtained compounds were evaluated for their anticonvulsant activity using PTZ and picrotoxin convulsive models. Compounds 47, 63, 68 and 73 proved to be the most active compounds in this study with a remarkable 100% protection against PTZ induced convulsions. Compounds 47, 63, 68 and 73 proved to be 10, 4, 4, and 5 fold more active, respectively than the used positive control sodium valproate. Structure activity correlation concluded valuable pharmacophoric information which confirmed by molecular modeling studies. Molecular docking study of 68 suggested its agonistic behavior toward GABAA receptor. The studied quinazoline analogues could be considered as useful templates for future development and further derivatization.
authors.affiliation: Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, PO Box 2457, Riyadh 11451, Saudi Arabia.
authors.forename: Huda S A
authors.initials: HS
authors.lastname: Al-Salem
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt.
authors.forename: Gehan H
authors.initials: GH
authors.lastname: Hegazy
authors.affiliation: Department of Pharmacology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia.
authors.forename: Kamal E H
authors.initials: KE
authors.lastname: El-Taher
authors.affiliation: Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt.
authors.forename: Shahenda M
authors.initials: SM
authors.lastname: El-Messery
authors.affiliation: Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, PO Box 2457, Riyadh 11451, Saudi Arabia.
authors.forename: Abdulrahman M
authors.initials: AM
authors.lastname: Al-Obaid
authors.affiliation: Department of Medicinal Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt; Department of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences & Pharmaceutical Industries, Future University, 12311 Cairo, Egypt. Electronic address: subbagh@yahoo.com.
authors.forename: Hussein I
authors.initials: HI
authors.lastname: El-Subbagh
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D006834:Hydrazines / Q000737:chemistry*; D051379:Mice; D008958:Models, Molecular; D015394:Molecular Structure; D010433:Pentylenetetrazole; D010852:Picrotoxin; D052999:Quinazolinones / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy*; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000737:chemistry*; D013890:Thiourea / Q000737:chemistry*
chemical_list: D000927:Anticonvulsants; D006834:Hydrazines; D010433:Pentylenetetrazole; D010852:Picrotoxin; D052999:Quinazolinones; D013449:Sulfonamides; D013890:Thiourea; C061339:4-hydroxyquinazoline
keywords: 4(3H)-Quinazolinones; Anticonvulsant activity; Molecular modeling study; Synthesis