Mardaneh Pegah, Lavian Salime, Bagherniya Mohammad, Roufogalis Basil, Sahebkar Amirhossein
Medicinal and Natural Products Chemistry Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
Department of Medicinal Chemistry, Faculty of Medicinal Chemistry, Shiraz University of Medical Sciences, Shiraz, Iran.
Curr Med Chem. 2024 Jan 23. doi: 10.2174/0109298673256932231123151626.
Treatment of cancer, one of the most fatal diseases in the present century, has become a topic of global concern. Unfavorable unintentional effects of chemotherapy and radiation treatments have been the main reasons for the research on the discovery of drugs with a broader spectrum of effectiveness and efficiency, with minimal side effects. Curcumin (diferuloylmethane) is a naturally occurring phenolic structure with anticancer properties through its inhibition of cell multiplication, metastasis, and prolongation of cell cycle suppression of apoptosis in various tumor cells. The primary restriction regarding the use of curcumin in cancer treatment is related to poor bioavailability and unfavorable pharmacokinetic profiles of curcumin due to its poor absorption rate, fast metabolism, and systemic elimination. A variety of ways have been proposed to overcome these limitations. With this background, the present study focuses on providing a comprehensive overview of the anticancer properties of curcumin derivatives and the synthesis of curcumin analogs with application to different types of cancers. The regulation of various target and signaling pathways is considered in various cancers, including breast, gastrointestinal, pancreatic, prostate, skin, and lung cancers. A review of the literature indicates that modifying the structure of curcumin through the substitution of the phenyl group and unsaturated carbon branch around the two main sites of oxygen can result in the improvement of physical and chemical properties, as well as the enhancement of physiological activities of the curcumin molecule and the anti-cancer activities of this polyphenol. Curcumin analogs demonstrate anticancer properties at multiple targets at different cell stages and by various signaling biochemical pathways. These include cytokines, transcription factors, growth factors, and modulation of genes involved in cellular proliferation and apoptosis in breast, gastrointestinal, skin, prostate, and lung cancers, thereby mitigating tumor progression.
癌症是本世纪最致命的疾病之一，其治疗已成为全球关注的话题。化疗和放疗产生的不良意外效应一直是人们研究发现疗效更广泛、效率更高且副作用最小的药物的主要原因。姜黄素（二阿魏酰甲烷）是一种天然存在的酚类结构，通过抑制细胞增殖、转移以及延长细胞周期来抑制各种肿瘤细胞的凋亡，从而具有抗癌特性。姜黄素在癌症治疗中应用的主要限制与其生物利用度差以及药代动力学特性不佳有关，这是由于其吸收率低、代谢快以及全身清除所致。人们已经提出了多种方法来克服这些限制。在此背景下，本研究着重全面概述姜黄素衍生物的抗癌特性以及姜黄素类似物的合成及其在不同类型癌症中的应用。研究考虑了包括乳腺癌、胃肠道癌、胰腺癌、前列腺癌、皮肤癌和肺癌在内的各种癌症中各种靶标和信号通路的调节。文献综述表明，通过在两个主要氧位点周围取代苯基和不饱和碳支链来修饰姜黄素的结构，可以改善其物理和化学性质，增强姜黄素分子的生理活性以及这种多酚的抗癌活性。姜黄素类似物在不同细胞阶段的多个靶标处以及通过各种信号生化途径表现出抗癌特性。这些包括细胞因子、转录因子、生长因子以及对乳腺癌、胃肠道癌、皮肤癌、前列腺癌和肺癌中参与细胞增殖和凋亡的基因的调节，从而减轻肿瘤进展。
