Document Type : Original Article
Authors
1
Chemistry Department, Faculty of Science, Menoufia University, Shebin El-Koam, 32511 Egypt
2
Faculty of Industrial Education, Beni Suef University, Beni Suef, 62512 Egypt
3
Chemistry Department, Faculty of Science, Arish University, Arish, 45511 Egypt
4
Medicinal Chemistry Department, Menoufia University, Shebin El-Koam, Egypt
5
Chemistry Department, Faculty of Science, Menoufia University, Shebin El-Koam, EGYPT.
Abstract
A novel series of quinazoline–amino acid hybrids has been synthesized through a multistep synthetic pathway. The synthesized compounds include ester derivatives (3, 4), hydrazide derivatives (5, 6, 13, 17), dipeptides (14–16), and tripeptides (18–20) of quinazoline. Their structures were confirmed via IR, ¹H-NMR, and ¹³C-NMR spectroscopy, along with elemental analysis. The antimicrobial evaluation revealed that all compounds exhibited moderate to strong activity, with compounds 4–6, 15, 16, and 18–20 displaying the most potent antibacterial and antifungal properties. Specifically, compound 6 demonstrated (39 mm, MIC = 8 µM, IC₅₀ = 7 µM) inhibition zone against Bacillus subtilis and (36 mm, MIC = 11 µM, IC₅₀ = 9 µM) inhibition against E. coli , and compound 4 showed strong activity against Escherichia coli with an inhibition of (33 mm, MIC = 13 µM, IC₅₀ = 11 µM). The antifungal activity was also notable, with compound 16 showing (13 mm, MIC = 35 µM, IC₅₀ = 28 µM) inhibition against Candida albicans. Furthermore, molecular docking studies highlighted their strong binding affinities to key microbial targets, with compound 19 exhibiting the top docking score (ΔG = –8.46 kcal/mol), compared to erlotinib (ΔG = –8.51 kcal/mol). In addition, the anticancer potential of the synthesized compounds was assessed in vitro against MCF7 breast cancer cells using the SRB assay. Compound 15 displayed significant cytotoxicity with an IC₅₀ value of 3.40 ± 0.13 µg/mL, demonstrating pharmacological performance comparable to doxorubicin (IC₅₀ = 2.97 ± 0.12 µg/mL). These findings underscore the promising therapeutic applications of quinazoline–amino acid hybrids, warranting further investigation into their biological mechanisms and clinical relevance.
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