In vitro and in silico characterization of angiogenic inhibitors from Sophora interrupta.
Sophora interrupta Bedd, (Fabaceae) is used in Indian folk medicine to treat cancer. Angiogenesis is one of the crucial characteristics of cancer metastasis and is regulated by vascular endothelial growth factor (VEGF). In this study, we examined the antiangiogenic properties of the root ethyl acetate extract of Sophora interrupta by various methods. In vitro antioxidant activity (100-600 μg/ml) of S. interrupta ethyl acetate (SEA) extract was evaluated by DPPH and ABTS, anti-inflammatory activity (50, 100 and 150 μg/ml) by estimating nitric oxide (NO) levels, anti-angiogenic activity (200 and 500 μg/ml) was validated by chorio allantoic membrane (CAM) assay and in silico molecular dynamic (MD) simulations analyses (25 ns) were performed to identify the anti-angiogenic compounds extracted from root extract. The antioxidative activity of SEA extract at IC50(200 ± 0.6 μg/mL) is equal to that of ascorbic acid at IC50(50 ± 0.6 μg/mL), and the anti-inflammatory activity of SEA extract at IC50(150 ± 0.2 μg/mL) was inhibited significantly by nitric oxide (NO) production. The SEA extract significantly reduced the sprouting of new blood vessels at ID50500 ± 0.13 μg/mL in the CAM assay. Gas chromatography-mass spectrometry analysis of the SEA extract detected 34 secondary metabolites, of which 6a,12a-dihydro-6H-(1,3)dioxolo(5,6)benzofuro(3,2-c)chromen-3-ol (maackiain) and funiculosin formed strong hydrogen bond interactions with Lys 920, Thr 916 and Cys 919 (2H), as well as Glu 917 of VEGFR2, and these interactions were similar to those of the anti-angiogenic compound axitinib. Significant findings in all the assays performed indicate that SEA extract has potential anti-angiogenic compounds that may interfere with VEGF-induced cancer malignancy.
Biomedical Research Laboratory, Department of Biotechnology, KLEF University (Koneru Lakshmaiah Educational Foundation), Green fields; Vaddeswaram, Guntur (Dist), 522502, Andhra Pradesh, India.|Upstream Process Development Team, Lupin Limited, Biotechnology R&D, 1156, Ghotawade Village, Mulshi Taluka, Pune-411042, India.
Pardhasaradhi
P
Mathi
Biomedical Research Laboratory, Department of Biotechnology, KLEF University (Koneru Lakshmaiah Educational Foundation), Green fields; Vaddeswaram, Guntur (Dist), 522502, Andhra Pradesh, India.
Ganesh Kumar
GK
Veeramachaneni
Biomedical Research Laboratory, Department of Biotechnology, KLEF University (Koneru Lakshmaiah Educational Foundation), Green fields; Vaddeswaram, Guntur (Dist), 522502, Andhra Pradesh, India.
K Kranthi
KK
Raj
Biomedical Research Laboratory, Department of Biotechnology, KLEF University (Koneru Lakshmaiah Educational Foundation), Green fields; Vaddeswaram, Guntur (Dist), 522502, Andhra Pradesh, India.
Venkateswara Rao
VR
Talluri
Department of Basic Sciences-Chemistry, Madanapalle Institute of Technology and Science (MITS), Madanapalle, Chittoor, 517325, Andhra Pradesh, India.
Venkata Raman
VR
Bokka
Biomedical Research Laboratory, Department of Biotechnology, KLEF University (Koneru Lakshmaiah Educational Foundation), Green fields; Vaddeswaram, Guntur (Dist), 522502, Andhra Pradesh, India. bmnchowdary@gmail.com.
Mahendran
M
Botlagunta
D020533:Angiogenesis Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000494:pharmacology; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line; D051379:Mice; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology; D018517:Plant Roots / Q000737:chemistry; D000067996:RAW 264.7 Cells; D029909:Sophora / Q000737:chemistry*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D020533:Angiogenesis Inhibitors; D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D010936:Plant Extracts; D042461:Vascular Endothelial Growth Factor A
Angiogenesis; Fabaceae; Mass spectroscopy; Molecular dynamic simulations
Dev Biol. 2012 Dec 15;372(2):157-65
23031691
J Med Chem. 2004 Mar 25;47(7):1739-49
15027865
Int J Mol Sci. 2013 May 02;14(5):9536-55
23644885
Chem Biol Drug Des. 2010 Apr;75(4):348-59
20331649
J Med Chem. 2004 Mar 25;47(7):1750-9
15027866
Pharmazie. 2013 May;68(5):369-75
23802436
Antioxidants (Basel). 2013 Jan 04;2(1):11-22
26787619
Biosci Trends. 2010 Apr;4(2):39-47
20448340
Bioinformation. 2014 Mar 19;10(3):144-51
24748754
ISRN Pharm. 2012;2012:195727
22830056
Biochem Pharmacol. 2006 Jan 12;71(3):307-18
16329999
Evid Based Complement Alternat Med. 2013;2013:131306
23970927
Mol Inform. 2013 Apr;32(4):385-98
27481595
Front Biosci. 2005 Jan 01;10:666-74
15569607
Cancer Sci. 2008 Aug;99(8):1501-6
18754859
J Chem Inf Model. 2013 Jul 22;53(7):1531-42
23782297
Oncol Rev. 2011 Sep;5(3):177-184
21949574
Expert Opin Biol Ther. 2007 Apr;7(4):449-60
17373897
Eur Urol. 2008 May;53(5):917-30
18054825
Cell. 1978 Sep;15(1):261-7
212198
ScientificWorldJournal. 2014 Jan 22;2014:967873
24587765
J Comput Chem. 2005 Dec;26(16):1752-80
16211539
J Biosci. 2011 Jun;36(2):341-54
21654087
Phytomedicine. 2001 Sep;8(5):395-400
11695884
Nat Prod Commun. 2012 Sep;7(9):1149-54
23074893
J Med Chem. 2004 Mar 25;47(7):1783-8
15027870
Cancer Cell. 2012 Mar 20;21(3):309-22
22439926