Truong Tuyen Ngoc, Canh Pham Em, Nguyen Tran Ngoc-Vi, Tieu Phu Thien, Thi Cao My Hanh, Hong Do Tuoi Thi, Le Khanh N B
School of Pharmacy, University of Medicine and Pharmacy at Ho Chi Minh City Ho Chi Minh City 700000 Vietnam
Faculty of Pharmacy, Hong Bang International University Ho Chi Minh City 700000 Vietnam.
RSC Adv. 2025 Aug 22;15(36):29864-29878. doi: 10.1039/d5ra03933a. eCollection 2025 Aug 18.
A series of 3-methylenamino-4(3)-quinazolone derivatives were synthesized by imine formation reactions of 3-amino-6-chloro-2-phenyl-4(3)-quinazolone with various substituted aromatic aldehydes at 80 °C for 1-3 hours using the reflux method. Twenty 3-methylenamino-4(3)-quinazolone derivatives were synthesized with good to excellent yields (66 to 90%). Compound 5 (2-chloro-6-fluorobenzylidene) exhibited good cytotoxic activity against the RD cell line with an IC value of 14.65 μM but exhibited weak cytotoxic activity against the MDA-MB-231 cell line (IC = 147.70 μM) compared to the reference drug paclitaxel (PTX, IC RD = 0.58 μM and IC MDA-MB-231 = 0.04 μM). Meanwhile, compounds 6 (benzo[][1,3]dioxol-5-ylmethylene) and 7 (4-bromo-2-hydroxybenzylidene) showed good cytotoxic activity against MDA-MB-231 with IC values of 10.62 and 8.79 μM, respectively. However, these compounds showed weak cytotoxic activity against the RD cell line (IC = 50-55 μM). In particular, potential compounds 5, 6, and 7 exhibited weak cytotoxic activity against the normal cell line LLC-PK1 (IC = 34.82-60.18 μM) compared to the highly toxic agent PTX (IC = 1.31 μM). Furthermore, compounds 5, 6, and 7 showed strong interactions with the EGFR target with binding affinities of -9.6, -10.1, and -9.8 kcal mol, respectively, compared to reference drug Gefitinib (-7.8 kcal mol). The ADMET results suggested that these potent derivatives possess a good ADMET profile. Therefore, these three compounds are potential candidates for novel cancer drug development, as demonstrated by and studies.
通过回流法，使3-氨基-6-氯-2-苯基-4(3)-喹唑啉酮与各种取代的芳香醛在80℃下反应1 - 3小时，通过亚胺形成反应合成了一系列3-亚甲基氨基-4(3)-喹唑啉酮衍生物。合成了20种3-亚甲基氨基-4(3)-喹唑啉酮衍生物，产率良好至优异（66%至90%）。化合物5（2-氯-6-氟亚苄基）对RD细胞系表现出良好的细胞毒性活性，IC值为14.65μM，但与参比药物紫杉醇（PTX，ICRD = 0.58μM和IC MDA-MB-231 = 0.04μM）相比，对MDA-MB-231细胞系表现出较弱的细胞毒性活性（IC = 147.70μM）。同时，化合物6（苯并[[1,3]二氧杂环戊烯-5-基亚甲基）和7（4-溴-2-羟基亚苄基）对MDA-MB-231表现出良好的细胞毒性活性，IC值分别为10.62和8.79μM。然而，这些化合物对RD细胞系表现出较弱的细胞毒性活性（IC = 50 - 55μM）。特别地，与高毒性药物PTX（IC = 1.31μM）相比，潜在化合物5、6和7对正常细胞系LLC-PK1表现出较弱的细胞毒性活性（IC = 34.82 - 60.18μM）。此外，与参比药物吉非替尼（-7.8 kcal mol）相比，化合物5、6和7与EGFR靶点表现出强烈的相互作用，结合亲和力分别为-9.6、-10.1和-9.8 kcal mol。ADMET结果表明这些强效衍生物具有良好的ADMET特性。因此，如 和 研究所示，这三种化合物是新型癌症药物开发的潜在候选物。
