Abstract

1,3-Bis-3-(4-chlorophenyl)-2,3-dihydroquinazolin-4(1H)-on-2-thioxopropane (C), a quinazoline derivative was synthesized and well-characterized in order to evaluate its potential to act as VEGFR-2 and Aurora kinase inhibitor. ¹H NMR, elemental analysis and FT-IR confirmed the structure of the synthesized compound (C). Since, VEGFR-2 plays a crucial role in angiogenesis, it is hence a significant pharmaceutical target for the development of anti-angiogenic agents. While on the other hand, AURKA is an enzyme that is believed to induce normal cell proliferation and is encoded with over-expression witnessed in various types of malignant cancers. The electrostatic potential and the molecular geometry of the conformers 1-3, was demonstrated by DFT calculations. The results of which, revealed that the syn conformer 3 was the most stable. The molecular docking studies gave a brief insight about the binding of the conformer 3, also suggesting its potential to act as dual inhibitor, that inhibits VEGFR-2 and Aurora kinase, thereby could play an important role in cancer inhibition.

摘要

1,3-Bis-3-(4-chlorophenyl)-2,3-dihydroquinazolin-4(1H)-on-2-thioxopropane ( C ) 是一种喹唑啉衍生物，并对其进行了充分表征，以评估其在作为 VEGFR-2 和 Aurora 激酶抑制剂。¹ H NMR、元素分析和FT-IR证实了合成化合物( C )的结构。由于 VEGFR-2 在血管生成中起着至关重要的作用，因此它是开发抗血管生成剂的重要药物靶点。另一方面，AURKA 是一种酶，被认为可诱导正常细胞增殖，并且在各种类型的恶性肿瘤中都存在过度表达。构象异构体的静电势和分子几何结构1-3，由 DFT 计算证明。结果表明，syn构象异构体3是最稳定的。分子对接研究简要介绍了构象异构体3的结合，也表明其作为双重抑制剂的潜力，可抑制 VEGFR-2 和 Aurora 激酶，从而在癌症抑制中发挥重要作用。