Karthik C S, Manukumar H M, Sandeep S, Sudarshan B L, Nagashree S, Mallesha L, Rakesh K P, Sanjay K R, Mallu P, Qin Hua-Li
Department of Chemistry , Sri Jayachamarajendra College of Engineering , Mysuru-570 006 , Karnataka , India . Email:
Department of Studies in Biotechnology , University of Mysore , Manasagangotri , Mysuru-570006 , Karnataka , India.
Medchemcomm. 2018 Apr 4;9(4):713-724. doi: 10.1039/c7md00628d. eCollection 2018 Apr 1.
Natural products are important leads in drug discovery. The search for effective plant-derived agents or their synthetic analogues has continued to be of interest to biologists and chemists for a long time. Herein, we have synthesized a novel compound, P1C, and P1C-TitCAgNPs from chitosan; P1C is a precursor and an anti-inflammatory candidate, which has been validated by molecular docking studies. The synthesized P1C-TitCAgNPs showed monodisperse, spherical, and cationic nature and antioxidant properties, protecting destabilization of the erythrocyte membrane by the azo compound 2,2'-azobis(2-amidinopropane)dihydrochloride (AAPH); the involvement of NPs as a protective agent for biomolecules, such as DNA and protein, followed by the treatment of NPs with AAPH was confirmed. The inhibition of cellular damage and leakage of cellular inflammatory agents was confirmed by AFM, SEM, TEM, SDS-PAGE, LDH, and PLA2 enzyme inhibition studies. The anti-inflammatory property of P1C was further validated by molecular docking studies and showed that, the P1C best pose aligned to PLA2 compared to standard drug. The significant anticancer property of P1C-TitCAgNPs was confirmed against MCF7, U373, and C6 cancer cell lines. Thus, the present study highlights the synthesized P1C in P1C-TitCAgNPs as a target PLA2-specific anti-inflammatory candidate, and further tuning of small and development-functionalized nanoparticles has a great future in medicine; hence, their clinical applications are warranted.
天然产物是药物发现中的重要先导物。长期以来，寻找有效的植物源药物或其合成类似物一直是生物学家和化学家感兴趣的课题。在此，我们从壳聚糖合成了一种新型化合物P1C和P1C-TitCAgNPs；P1C是一种前体和抗炎候选物，已通过分子对接研究得到验证。合成的P1C-TitCAgNPs表现出单分散、球形和阳离子性质以及抗氧化性能，可保护红细胞膜免受偶氮化合物2,2'-偶氮二(2-脒基丙烷)二盐酸盐(AAPH)的破坏；证实了纳米颗粒作为生物分子（如DNA和蛋白质）保护剂的作用，随后用AAPH处理纳米颗粒。通过原子力显微镜(AFM)、扫描电子显微镜(SEM)、透射电子显微镜(TEM)、十二烷基硫酸钠-聚丙烯酰胺凝胶电泳(SDS-PAGE)、乳酸脱氢酶(LDH)和磷脂酶A2(PLA2)酶抑制研究证实了对细胞损伤的抑制和细胞炎症介质的泄漏。P1C的抗炎特性通过分子对接研究进一步得到验证，结果表明，与标准药物相比，P1C的最佳构象与PLA2对齐。证实了P1C-TitCAgNPs对MCF7、U373和C6癌细胞系具有显著的抗癌特性。因此，本研究强调了P1C-TitCAgNPs中合成的P1C作为靶向PLA2特异性抗炎候选物的作用，进一步调整小型和开发功能化纳米颗粒在医学上具有广阔的前景；因此，它们的临床应用是有必要的。
