Adhikari Hari Sharan, Yadav Paras Nath
Department of Chemistry, Western Region Campus, Institute of Engineering, Tribhuvan University, Pokhara, Nepal.
Central Department of Chemistry, Tribhuvan University, Kathmandu, Nepal.
Int J Biomater. 2018 Dec 30;2018:2952085. doi: 10.1155/2018/2952085. eCollection 2018.
Tailoring of chitosan through the involvement of its amino, acetamido, and hydroxy groups can give derivatives of enhanced solubility and remarkable anticancer activity. The general mechanism of such activity is associated with the disturbances in normal functioning of cell cycle, interference to the central dogma of biological system from DNA to RNA to protein or enzymatic synthesis, and the disruption of hormonal path to biosynthesis to inhibit the growth of cancer cells. Both chitosan and its various derivatives have been reported to selectively permeate through the cancer cell membranes and show anticancer activity through the cellular enzymatic, antiangiogenic, immunoenhancing, antioxidant defense mechanism, and apoptotic pathways. They get sequestered from noncancer cells and provide their enhanced bioavailability in cancer cells in a sustained release manner. This review presents the putative mechanisms of anticancer activity of chitosan and mechanistic approaches of structure activity relation upon the modification of chitosan through functionalization, complex formation, and graft copolymerization to give different derivatives.
通过壳聚糖的氨基、乙酰氨基和羟基进行修饰,可以得到溶解性增强且具有显著抗癌活性的衍生物。这种活性的一般机制与细胞周期正常功能的紊乱、对从DNA到RNA再到蛋白质或酶合成的生物系统中心法则的干扰以及激素生物合成途径的破坏以抑制癌细胞生长有关。据报道,壳聚糖及其各种衍生物都能选择性地透过癌细胞膜,并通过细胞酶促、抗血管生成、免疫增强、抗氧化防御机制和凋亡途径表现出抗癌活性。它们从非癌细胞中分离出来,并以持续释放的方式在癌细胞中提供更高的生物利用度。本文综述了壳聚糖抗癌活性的推测机制,以及通过功能化、络合形成和接枝共聚修饰壳聚糖以得到不同衍生物时的构效关系机制方法。