Design, Synthesis and Anticancer Evaluation of New 7-O-Alkylation Genistein Derivatives
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Pharmaceutical Chemistry Journal, Vol. 54, No. 9, December, 2020 (Russian Original Vol. 54, No. 9, September, 2020)
DESIGN, SYNTHESIS AND ANTICANCER EVALUATION OF NEW 7-O-ALKYLATION GENISTEIN DERIVATIVES Yuyan Ren,1,2,3,** Hongfei Chen,1,2,3,** Xu Yao,1,2,3 Zehua Yang,1,2,3 Tingjuan Wu,1,2,3 Yu Guo,1,2 Junhui Xiao,1,2 and Xing Zheng1,2,3,* Original article submitted October 27, 2019. Genistein is a phytoestrogen compound which possesses multiple biological activities such as anti-cancer, while its application is limited by poor pharmacokinetic properties. Structural modification is an effective approach to get genistein derivatives with better activities and approved pharmacokinetic properties. Based on previous research work, we synthesized two series of genistein derivatives bearing halogen substituents, and evaluated their inhibitory effects on the cancer cell lines MCF-7, MDA-MB-231, and MDA-MB-435. Among these derivatives, compound XI displayed the best inhibitory activity against MCF-7, MDA-MB-231 and MDA-MB-435 cell lines in vitro, which is worth further studies. Keywords: genistein derivatives; isoflavone; anticancer activity; MTT assay; synthesis.
vivo instability, and poor solubility [13]. Up to now, numerous research works have studied the structure activity relationship of genistein and its derivatives, in the hope of getting potent anti-cancer agents through structural modification [14 – 16]. Our group had previously designed and synthesized several series of flavone derivatives and carried out their activity evaluation in vitro and in vivo, which showed that many of them possessed potent anticancer activity [17 – 19]. Inspired by the previous research work, we have designed and synthesized two series of genistein derivatives and evaluated their anticancer activity in vitro against MCF-7, MDA-MB-231, and MDA-MB-435 cell lines.
1. INTRODUCTION Breast cancer is the fifth leading cause of cancer-related death worldwide and the second leading cause of cancer death among women, accounting for approximately 626679 deaths in 2018 [1]. It is noteworthy that the breast cancer morbidity in some Asian countries such as China and Japan is on a relatively lower level [2]. This is probably related with Asian peoples having high consumption of beans that are rich in flavonoids. As a member of plant polyphenols, the flavonoid phenol groups in their structures may contribute to their anticancer activity [3]. Genistein (4¢,5,7-trihydroxyisoflavone) is an isoflavonoid compound widely distributed in plants [4, 5], which had been emphasized by more than 3600 papers in the past decade because of its multiple biological effects such as the anticancer effect [6 – 9] and especially anti-breast cancer activity [19, 11]. Genistein is also a phytoestrogen due to its structural features similar to those of estradiol-17b estrogen [12]. However, the application of genistein is limited because of its structural characteristics, susceptibility to oxidation, in
2. RESULTS AND DISCUSSION 2.1. Chemistry All the new genistein derivati
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