In-vitro immunomodulatory and anti-cancerous activities of biotransformed products of Dianabol through Azadirachta indica and its molecular docking studies.
BACKGROUND
Plant Biotransformation is one of the tools for structural modifications of the organic substrate of low, moderate or high biological value utilizing plant cultured cells, these modifications of organic structures may lead to biologically augmented products and which may be ultimately substantial in cure or improvement of various morbidities and diseases.


RESULTS
Azadirachta indica A. Juss. suspension culture was employed for the biotransformation of dianabol (1) for the first time, and two metabolites, 17β-hydroxy-17α-methyl-5α-androst-1-en-3-one (2), and 17β-hydroxy-17α-methyl-5α-androstan-3-one (3) were obtained.


CONCLUSIONS
Most important aspect of this work was the evaluation of metabolite 2, which strongly and differentially suppressed [not affecting whole blood and human polymorphonuclear cells (PMN)] the phytohemagglutinin (PHA)-activated T-cell proliferation (IC50: <10.33 μM), and also found to inhibit IL-2 production (IC50: 16.89 ± 1.32) unlike metabolite 3 and compound 1. Compound 2 also exhibited anticancer activity against lung cancer cell line; NCI-H460, it moderately inhibited the growth of cancer cells (22.5 ± 4.15 μM). Furthermore, a good correlation between the predicted binding energies of the compounds acquired by the FlexX program and the experimental affinities were speculated upon interacting with IL-2 protein during molecular docking studies.
Department of Biotechnology, Faculty of Science, University of Karachi, Karachi 75270, Pakistan.
Saifullah
Department of Biotechnology, Faculty of Science, University of Karachi, Karachi 75270, Pakistan.
Saifullah
S
Khan
Department of Chemistry, Federal Urdu University for Arts, Science & Technology, Gulshan-e-Iqbal Campus, Karachi 75300, Pakistan.
Azizuddin
Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan.
Sobia Ahsan
SA
Halim
Department of Biotechnology, Faculty of Science, University of Karachi, Karachi 75270, Pakistan.
Muhammad
M
Kashif
Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan.
Almas
A
Jabeen
Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan.
Muhmammad
M
Asif
Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan.
Muhammad Ahmed
MA
Mesaik
Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan.
Zaheer
Z
Ul-Haq
Department of Biotechnology, Faculty of Science, University of Karachi, Karachi 75270, Pakistan ; Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan.
Ahsana
A
Dar
Department of Biotechnology, Faculty of Science, University of Karachi, Karachi 75270, Pakistan ; Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan.
Muhammad Iqbal
MI
Choudhary
Anti-cancer activity; Anti-inflammatory activity; Biotransformation; Molecular docking studies