Synthesis, antimicrobial evaluation and docking studies of some novel quinazolinone Schiff base derivatives

Abstract

The quinazolin-4(3H)-one structural motif possesses a wide spectrum of biological activities. DNA gyrase play an important role in induction of bacterial death. It has been shown that many quinazolin-4(3H)-one derivatives have antibacterial effects through inhibition of DNA gyrase. Based on this information we decided to synthesize novel quinazolinone Schiff base derivatives in order to evaluate their antibacterial effects. A series of novel quinazolinone Schiff base derivatives were designed and synthesized from benzoic acid. The potential DNA gyrase inhibitory activity of these compounds was investigated using in silico molecular docking simulation. All new synthesized derivatives were screened for their antimicrobial activities against three species of Gram-negative bacteria including Escherichia coli, Pseudomonas aeruginosa, Salmonella entritidis and three species of Gram-positive bacteria comprising of Staphylococcus aurous, Bacillus subtilis, Listeria monocitogenes as well as for antifungal activities against Candida albicans using the conventional micro dilution method. Most of the compounds have shown good antibacterial activities, especially against E. coli at 128 µg/mL concentration while no remarkable antifungal activities were observed for these compounds. All the synthesized compounds exhibit dock score values between -5.96 and -8.58 kcal/mol. The highest dock score among them was -8.58 kcal/mol for compound 4c.

Synthesis and cytotoxic evaluation of some derivatives of triazole-quinazolinone hybrids

“…In view of valuable cytotoxic effects of both triazoles and quinazolinones and in continuation of our previous research on quinazolinone derivatives (23456789), it seemed most interesting to synthesize derivatives of quinazolinone bearing triazole group as enhancing moiety for cytotoxic activity.…”

“…Although there have been great advances in the treatment of cancer, due to the complications associated with clinical use of anticancer drugs such as drug resistance, side effects, and systemic toxicity, discovering various chemical structures with high efficacy and minimum undesirable side effects is very important (1). Quinazolinone as an important pharmacophore in medicinal chemistry has drawn much attention due to its wide range of biological effects, which include antibacterial, antifungal, anticancer, anti-inflammatory, and antihypertensive activities (234567). Different mechanisms such as inhibition of the DNA repair enzyme, inhibition of epidermal growth factor receptor (EGFR), thymidylate enzyme inhibition and inhibitory effects for tubulin polymerize have been proposed for anticancer activities of quinazolinone-based structures (89).…”

Synthesis and cytotoxic evaluation of some quinazolinone- 5-(4-chlorophenyl) 1, 3, 4-oxadiazole conjugates

“…The proposed anticancer mechanisms for oxadiazoles include inhibition of tubulin polymerization and epidermal growth factor receptor (EGFR). Quinazolinone is another nitrogenated scaffold that was extensively used in drug development programs and its derivatives showed diverse biological activities as anticancer, antifungal, anti-inflammatory, and antimicrobial (9101112131415). Quinazolinone-based structures exert their anticancer activity through different mechanisms including inhibition of the DNA repair enzyme system, inhibition of EGFR (9), thymidylate enzyme inhibition, and inhibitory effects for tubulin polymerize (14).…”

“…Because of the remarkable cytotoxic effects of 1, 3, 4-oxadiazole (678) and quinazolinone (910111213) derivatives, and in the hope of achieving synergistic response due to the presence of both quinazolinone and 1,3,4-oxadiazole moieties, in this study, some of new quinazoline derivatives containing the 1, 3, 4-oxadiazole were synthesized and evaluated for their cytotoxic activity.…”

Exploring the interaction between epidermal growth factor receptor tyrosine kinase and some of the synthesized inhibitors using combination of in-silico and in-vitro cytotoxicity methods

“…In two previous studies, our research group have synthesized 4-anilinoquinazoline and 4(3H)-quinazolinones Schiff base derivatives reporting the antimicrobial activity(1112). As explained above, these derivatives may be regarded as new inhibitors of human EGFR(45789).…”