Ali Gamal Al-kaf
Sana University, Yemen
Ali Gamal Al-kaf is a professor in Sana University, Yemen
In this study, four new compounds of quinazolinone-4 derivatives were synthesized and evaluated for some of their pharmacological activities that were predicted by computer program (PASS), and also testified for their yield obtained by using some of strong polar aprotic solvents. The new compounds were synthesized in the lab by allowing interaction of 2-phenylbenzoxazinones-4 with p-aminobenzenesulfonamides in a medium of acid catalyst and strong polar aprotic solvents (DMSO or DMFA). In the pharmacological studies, the synthesized compounds have been investigated for their toxicity, antihypoxic (in vivo), analgesic & anti-inflammatory (in vivo by testing reduction in licking response and inhibition of edema induced by formalin), and antimalarial activity (in vitro). The results showed that using of catalytic quantity of the strong polar aprotic solvents increased the yield by 25% with DMSO and 12.5% with DMFA. The pharmacological studies approved that the new compounds have low toxicity; since compounds (A, B & C) gave calss VI (harmless) and compound D gave class V (practically non toxic) according to Sidorov’s classification. In the antihypoxic study, the investigated compounds (B & D) showed high antihypoxic activity, 29.08% & 48.2% respectively higher than the compared standard piracetam. The investigated compounds (A & C) showed high analgesic and anti-inflammatory activity. Analgesic activity was increased by 26% & 186% respectively compared with the standard diclofenac while the anti-inflammatory activity was increased by 26% & 186% respectively compared with the standard diclofenac. For the antimalarial activity, the investigated compounds (B & D) inhibited the maturation of ring form of plasmodium falciparum to schizont form, (in vitro) test and showed high antimalarial activity compared with chloroquin. In-vitro study of compounds (A, B, C & D) shows no antibacterial activity. We suggest that the activity will be shown clearly in experiments in vivo, because these compounds will be metabolized into the corresponding sulfonamides. In the anti-oxidant study, the investigated compounds (B & D) showed high anti-oxidant activity, 29.08% & 48.2% respectively higher than the compared standard liv-52. We concluded from our study that the new synthesized quinazolinone-4 derivatives were preferably obtained with usage of strong polar aprotic solvents especially DMSO. In addition, the pharmacological investigations have confirmed the prediction of PASS that testifies the high reliability of the obtained results.