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Antiproliferative, antioxidant and binding mechanism analysis of prodigiosin from newly isolated radio-resistant Streptomyces sp. strain WMA-LM31

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Abstract

Streptomyces genus are filamentous Gram positive bacteria, of great intrest, producing biologically active compounds. Recent market and consumer curiosity in natural products have forced scientist and industry for the development of new products with therapeutic potential. This study focuses on evaluation of antioxidant and anticancerous properties of prodigiosin from radio-resistant Streptomyces sp. strain WMA-LM31. A molecular docking approach was adopted to understand theoretical binding mechanism and affinity for anticancer targets. A radio-resistant bacterium, labelled as strain WMA-LM31, was isolated from desert soil and screened for its radio-resistant potential and prodigiosin production. 16S rRNA gene sequencing showed that the bacterium clusters to genus Streptomyces and found resistant to ultraviolet radiation (dosage of 2 × 103 J/m2). Strain WMA-LM31 produced a red color pigment in tryptone glucose yeast (TGY) medium.The LC–MS analysis of the purified compound showed a molar mass of 324 [m/z]+ matched the chemical formula C20H25N3O, identified as prodigiosin. The compound showed strong antioxidant (62.51%) activities along with significant inhibitory action against oxidative damages to bovine serum albumin (BSA) and mice liver lipids in comparison to standard ascorbic acid. IC50 values of HepG2 and HeLa cell lines was found at 12.66 and 14.83 µg/mL of prodigiosin concentration, respectively. Furthermore, molecular docking was performed with two different cancers macromolecular targets: [2O2F (Bcl-2) and 1DI8 (CDK-2)], and BSA (PDB id: 3V03). The results indicated that the binding affinity of prodigiosin to its target molecules is due to the presence of terminal pyrrole rings. It is concluded from the results that prodigiosin from Streptomyces sp. strain WMA-LM31 has strong antioxidant, anticancer and apoptotic properties. The knowledge of binding mechanisms and interactions of prodigiosin could provide future directions in designing potent target specifc drugs.

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Acknowledgements

This work was supported by grants from Higher Education Commission of Pakistan under International Research Support Initiative Program (IRSIP). We also highly acknowledge McPhail Lab, Department of Pharmaceutical Sciences, Oregon State University, USA, for providing the opportunity to work in collaboration. We also acknowledge the contribution of Biochemistry Laboratory, Quaid-I-Azam University Islamabad, Pakistan by providing equipment facilities in bioassay studies.

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Authors and Affiliations

  1. Department of Microbiology, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, 45320, Pakistan

    Wasim Sajjad, Fariha Hasan & Aamer Ali Shah

  2. Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, Corvallis, OR, 97331, USA

    Wasim Sajjad

  3. Department of Multidisciplanary Studies, National University of Medical Sciences, Rawalpindi, 46000, Pakistan

    Wasim Sajjad

  4. Computational Biology Lab, National Center for Bioinformatics, Quaid-i-Azam University, Islamabad, 45320, Pakistan

    Sajjad Ahmad & Syed Sikander Azam

  5. Department of Chemistry, Faculty of Natural Sciences, Quaid-i-Azam University, Islamabad, 45320, Pakistan

    Iffat Aziz

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Correspondence to Aamer Ali Shah.

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Sajjad, W., Ahmad, S., Aziz, I. et al. Antiproliferative, antioxidant and binding mechanism analysis of prodigiosin from newly isolated radio-resistant Streptomyces sp. strain WMA-LM31. Mol Biol Rep 45, 1787–1798 (2018). https://doi.org/10.1007/s11033-018-4324-3

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