Synthesis and Antitumor Activity of Novel Isolongifolic-Alkyl Dihydropyrimidinethione Derivatives

Abstract

NMR、 13 C NMR 及高分辨质谱(HRMS)对其结构进行了表征, 通过 X 射线衍射分析测定了化合物 3e 的晶体结构. 探索 了这些衍生物对人乳腺癌细胞(MDA-MB-231)、人宫颈癌细胞(HeLa)、人肝癌细胞(HepG-2)等三种癌细胞和一种正常 细胞即小鼠巨噬细胞(RAW-264.7)的体外抗增殖活性. 结果表明, 这 12 种化合物显示出较好的抗肿瘤活性, 其 IC 50 值在 3.12～44.28 μmol/L 范围内. 其中, 化合物 3j 对 MDA-MB-231 细胞表现出最强的抗肿瘤活性(IC 50 ＝3.12 μmol/L), 化合 物 3g 对 HeLa 细胞表现出最强的抗肿瘤活性(IC 50 ＝4.04 μmol/L), 化合物 3k 对 HepG-2 细胞表现出最强的抗肿瘤活性 (IC 50 ＝5.43 μmol/L). 此外, 化合物 3j 将 MDA-MB-231 细胞阻滞在 G0/G1 期, 并以剂量依赖的方式诱导 MDA-MB-231 细胞的早期凋亡.

Synthesis and antitumor activity of isolongifoleno[7,8‐d]thiazolo[3,2‐a]pyrimidine derivatives via enhancing ROS level

“…The synthetic route of target compounds is shown in Scheme 1 7‐Arylmethylene isolongifolanones ( 2a – 2f ) were obtained by the reaction of isolongifolanone ( 1 ) and substituted benzaldehydes in tert ‐butyl alcohol according to the previously reported methods (Rui et al., ). Compounds 2a – 2f were further reacted with thiourea to get compounds 3a – 3f (Ma et al., ), and the target compounds 4a – 4x were obtained by cyclization of compounds 3a – 3f and substituted 2‐bromoacetophenones. The structures of 4a – 4x were confirmed by 1 H NMR, 13 C NMR and high‐resolution mass spectrometry (HRMS).…”

“…Compounds 3a – 3f were synthesized according to the literature (Ma et al., ). To a solution of compounds 2a – 2f (6 mmol) in 40 ml of ethanol and 60 ml of tert ‐butyl alcohol was added thiourea (7 mmol) and potassium tert ‐butoxide (12 mmol).…”

“…Isolongifolanone can be obtained from longifolene by oxidation reaction (Prahlad, Nayak, & Dev, ; RamdasNayak & Sukh, ) which is also extensively used in many pharmaceutical and perfumery industries (Panten, Bertram, & Surburg, ; Pybus, Sell, & Pybus, ). Isolongifolanone can also convert to other various derivatives which have many biological activities (Wang et al., , ) especially antitumor activity (Ma et al., ; Rui et al., , ).…”