Department of Chemistry, Assam University, Silchar, Assam, 788011, India.
Faculty of Life Sciences and Biotechnology, South Asian University, New Delhi, 110021, India.
Eur J Med Chem. 2019 Jul 15;174:66-75. doi: 10.1016/j.ejmech.2019.04.051. Epub 2019 Apr 20.
Two Zn(II) nitro porphyrin derivatives bearing combinations of meso-4-nitrophenyl and meso-4-methylpyridinium moieties and their free-base precursors were synthesized through one-pot microwave process, purified and characterized. The biological activity of these nitroporphyrins was assessed under both photodynamic and non-photodynamic conditions to correlate their structure-activity relationship (SAR). Unlike, the free-base precursors, Zn(II) complexes of these nitroporphyrins displayed nearly complete inhibition in the entry of lentiviruses such as HIV-1 and SIVmac under non-photodynamic conditions. In addition, the Zn(II) complexes also exhibited a higher in vitro photodynamic activity towards human lung cancer cell-line A549 than their free-base precursors. Our results strongly suggest that incorporation of Zn(II) has improved the antiviral and anticancer properties of the nitroporphyrins. To the best of our knowledge, this is the first report demonstrating the dual activity of nitroporphyrin-zinc complexes as antiviral and anti-cancer, which will aid in their development as therapeutics in clinics.
通过一锅微波法合成了两种带有间-4-硝基苯基和间-4-甲基吡啶鎓部分组合的锌(II)硝基卟啉衍生物及其自由碱基前体，并对其进行了纯化和表征。在光动力和非光动力条件下评估了这些硝基卟啉的生物活性，以关联它们的结构-活性关系 (SAR)。与自由碱基前体不同，这些硝基卟啉的锌(II)配合物在非光动力条件下几乎完全抑制了 HIV-1 和 SIVmac 等慢病毒的进入。此外，锌(II)配合物对人肺癌细胞系 A549 的体外光动力活性也高于其自由碱基前体。我们的结果强烈表明，锌(II)的掺入提高了硝基卟啉的抗病毒和抗癌特性。据我们所知，这是首次报道证明了硝基卟啉-锌配合物的双重抗病毒和抗癌活性，这将有助于它们在临床上作为治疗药物的开发。
