The study aimed to evaluate the
antioxidant,
protein kinase inhibitory (PKIs) potential, cytotoxicity activity of Streptomyces clavuligerus extract. DPPH assay revealed a robust
free radical scavenging capacity (IC50 28.90 ± 0.24 µg/mL) of organic extract with a maximum inhibition percentage of 61 ± 1.04%. PKIs assay revealed the formation of a whitish bald zone by S. clavuligerus extracts which indicates the presence of PKIs. The cytotoxicity activity of organic fraction of extract through
Sulforhodamine B assay on MCF-7, Hop-62, SiHa, and PC-3 cell lines demonstrated the lowest GI50 value against the MCF-7 cell line followed by the PC-3 cell line, showing potent growth inhibitory potential against human
breast cancer and human
prostate cancer cell line. HR-LCMS analysis identified multiple secondary metabolites from the organic and aqueous extracts of S. clavuligerus when incubated at 30°C under 200 rpm for 3 days. All the secondary metabolites were elucidated for their potential to inhibit RTKs by molecular docking, molecular dynamic simulation, MM/GBSA calculations, and free energy approach. It revealed the superior inhibitory potential of
epirubicin (Epi) and dodecaprenyl
phosphate-
galacturonic acid (DPGA) against
fibroblast growth factors receptor (FGFR). Epi also exhibited excellent inhibitory activity against the
platelet-derived growth factor receptor (PDGFR), while DPGA effectively inhibited the
vascular endothelial growth factor receptor. Additionally, the presence Epi in S. clavuligerus extract was validated through the HPLC technique. Thus, our findings highlight a superior inhibitory potential of Epi against FGFR and PDGFR RTKs than the FDA-approved
drug.