Flavonoids as a scaffold for development of novel anti-angiogenic agents: An experimental and computational enquiry.
Relationship between structural diversity and biological activities of flavonoids has remained an important discourse in the mainstream of flavonoid research. In the current study anti-angiogenic, cytotoxic, antioxidant and cyclooxygenase (COX) inhibitory activities of diverse class of flavonoids including hydroxyl and methoxy substituted flavones, flavonones and flavonols have been evaluated in the light of developing flavonoids as a potential scaffold for designing novel anti-antiangiogenic agents. We demonstrate anti-angiogenic potential of flavonoids using in vivo chorioallantoic membrane model (CAM) and further elaborate the possible structural reasoning behind observed anti-angiogenic effect using in silico methods. Additionally, we report antioxidant potential and kinetics of free radical scavenging activity using DPPH and SOR scavenging assays. Current study indicates that selected flavonoids possess considerable COX inhibition potential. Furthermore, we describe cytotoxicity of flavonoids against selected cancer cell lines using MTT cell viability assay. Structural analysis of in silico docking poses and predicted binding free energy values are not only in accordance with the experimental anti-angiogenic CAM values from this study but also are in agreement with the previously reported literature on crystallographic data concerning EGFR and VEGFR inhibition.
School of Life Sciences, Swami Ramanand Teerth Marathwada University, Nanded 431 606, MS, India. Electronic address: rngacche@rediffmail.com.
R N
RN
Gacche
School of Life Sciences, Swami Ramanand Teerth Marathwada University, Nanded 431 606, MS, India.
R J
RJ
Meshram
School of Life Sciences, Swami Ramanand Teerth Marathwada University, Nanded 431 606, MS, India.
H D
HD
Shegokar
Department of Microbiology, Savitribai Phule Pune University, Pune 411007, MS, India.
D S
DS
Gond
School of Life Sciences, Swami Ramanand Teerth Marathwada University, Nanded 431 606, MS, India.
S S
SS
Kamble
School of Life Sciences, Swami Ramanand Teerth Marathwada University, Nanded 431 606, MS, India.
V N
VN
Dhabadge
National Center for Cell Sciences, Pune 411007, MS, India.
B G
BG
Utage
School of Life Sciences, Swami Ramanand Teerth Marathwada University, Nanded 431 606, MS, India.
K K
KK
Patil
School of Life Sciences, Swami Ramanand Teerth Marathwada University, Nanded 431 606, MS, India.
R A
RA
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D020533:Angiogenesis Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology; D000975:Antioxidants / Q000737:chemistry* / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002645:Chickens; D016861:Cyclooxygenase Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D015195:Drug Design; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000378:metabolism; D005419:Flavonoids / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D008958:Models, Molecular; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors / Q000378:metabolism
D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D000975:Antioxidants; D016861:Cyclooxygenase Inhibitors; D005419:Flavonoids; D066246:ErbB Receptors; D040262:Receptors, Vascular Endothelial Growth Factor
Anti-angiogenesis; Antioxidant; Cyclooxygenase inhibition; Cytotoxicity; Flavonoids; Molecular docking; VEGFR and EGFR