Ugwu David Izuchukwu, Conradie Jeanet
Department of Chemistry, University of the Free State, South Africa; Department of Pure and Industrial Chemistry, University of Nigeria, Nsukka, Nigeria.
Department of Chemistry, University of the Free State, South Africa.
J Inorg Biochem. 2023 Sep;246:112268. doi: 10.1016/j.jinorgbio.2023.112268. Epub 2023 Jun 1.
Cancer is the abnormal division and multiplication of cells in an organ or tissue. It is the second leading cause of death globally. There are various types of cancer such as prostate, breast, colon, lung, stomach, liver, skin, and many others depending on the tissue or organ where the abnormal growth originates. Despite the huge investment in the development of anticancer agents, the transition of research to medications that improve substantially the treatment of cancer is less than 10%. Cisplatin and its analogs are ubiquitous metal-based anticancer agents notable for the treatment of various cancerous cells and tumors but unfortunately accompanied by large toxicities due to low selectivity between cancerous and normal cells. The improved toxicity profile of cisplatin analogs bearing bidentate ligands has motivated the synthesis of vast metal complexes of bidentate ligands. Complexes derived from bidentate ligands such as β-diketones, diolefins, benzimidazoles and dithiocarbamates have been reported to possess 20 to 15,600-fold better anticancer activity, when tested on cell lines, than some known antitumor drugs currently on the market, e.g. cisplatin, oxaliplatin, carboplatin, doxorubicin, and 5-fluorouracil. This work discusses the anticancer properties of various metal complexes derived from bidentate ligands, for possible application in chemotherapy. The results discussed were evaluated by the IC values as obtained from cell line tests on various metal-bidentate complexes. The structure-activity relationship study of the complexes discussed, revealed that hydrophobicity is a key factor that influences anticancer properties of molecules.
癌症是器官或组织中细胞的异常分裂和增殖。它是全球第二大死因。癌症有多种类型，如前列腺癌、乳腺癌、结肠癌、肺癌、胃癌、肝癌、皮肤癌等，具体取决于异常生长发生的组织或器官。尽管在抗癌药物研发方面投入巨大，但从研究到能大幅改善癌症治疗的药物的转化率不到10%。顺铂及其类似物是普遍使用的金属基抗癌药物，以治疗各种癌细胞和肿瘤而闻名，但不幸的是，由于癌细胞与正常细胞之间的选择性低，它们伴有较大的毒性。含双齿配体的顺铂类似物改善的毒性特征促使人们合成了大量双齿配体的金属配合物。据报道，从双齿配体如β-二酮、二烯烃、苯并咪唑和二硫代氨基甲酸盐衍生的配合物，在细胞系测试中，其抗癌活性比目前市场上一些已知的抗肿瘤药物，如顺铂、奥沙利铂、卡铂、阿霉素和5-氟尿嘧啶，高20到15600倍。这项工作讨论了从双齿配体衍生的各种金属配合物的抗癌特性，以便在化疗中可能应用。所讨论的结果通过对各种金属-双齿配合物进行细胞系测试获得的IC值进行评估。对所讨论的配合物的构效关系研究表明，疏水性是影响分子抗癌特性的关键因素。
