School of Pharmaceutical Sciences, Rajiv Gandhi Proudyogiki Vishwavidyalaya, Airport Bypass Road, Gandhi Nagar, Bhopal-462036, Madhya Pradesh, India.
Med Chem. 2009 Nov;5(6):549-57. doi: 10.2174/157340609790170533.
Cancer is one of the life threatening diseases and the development of novel anticancer molecules is limited by many reasons. In the present investigation, some novel benzo[a]phenazine-5-sulfonic acid derivatives as DNA intercalator was designed with optimized pharmacokinetic features for cancer treatment. The compounds with desired pharmacokinetic profile were synthesized and structurally characterized. Cytotoxic activity study against HL-60 tumor cell lines shows that 10-dimethyl carboxamido derivative of benzo[a]phenazine-5-sulfonic acid is found to be the most active in the series with cytotoxic activity (IC(50) = 19 microM) comparable to cisplatin (IC(50) = 7 microM). The study concluded that the novel benzo[a]phenazine-5-sulfonic acid derivatives were found to have enhanced DNA binding affinity and exhibited significant activity in vitro against HL-60 cell lines. This work will also guide for further development of effective DNA intercalators for cancer treatment.
癌症是一种威胁生命的疾病，新型抗癌分子的发展受到多种原因的限制。在本研究中，设计了一些新型苯并[a]吩嗪-5-磺酸衍生物作为 DNA 嵌入剂，具有优化的药代动力学特征，用于癌症治疗。合成并结构表征了具有所需药代动力学特征的化合物。对 HL-60 肿瘤细胞系的细胞毒性活性研究表明，苯并[a]吩嗪-5-磺酸的 10-二甲基氨基甲酰基衍生物在该系列中具有最高的活性，其细胞毒性活性（IC50=19 μM）可与顺铂（IC50=7 μM）相媲美。研究结论认为，新型苯并[a]吩嗪-5-磺酸衍生物具有增强的 DNA 结合亲和力，并在体外对 HL-60 细胞系表现出显著的活性。这项工作也将为进一步开发有效的用于癌症治疗的 DNA 嵌入剂提供指导。
