In silico Pharmacological Screening of Nitrogen containing Bisphosphonate Conjugate with Hydroxyapatite Active Constituents in Finding Potent Inhibitors for Bone Related Diseases

Osteoporosis is a skeletal disease-causing bone fragility by disturbing micro architecture of the bone leading to osteoclasts mediated bone loss. Inhibition of the Farnesyl Pyrophosphate Synthase (FPPS) of mevalonate pathway and Receptor Activator of Nuclear factor kappa-Β ligand (RANKL/OPG) complex by using anti resorptive drugs like Nitrogen containing Bisphosphonates aid in the effective treatment of osteoporosis. The in-silico docking analysis of newly synthesized Ibandronate– hydroxyapatite conjugate has shown as a most powerful binary to HMG-COA Reductase, Farnesyl pyrophosphate synthase (FPPS), Human Geranyl Geranyl pyrophosphate synthase (GPPS) & RANKL/OPG in contrast to pure Ibandronate. The docking score of Ibandronate hydroxyapatite (IBA-HAP) was found to be -6.12, -6.75, -5.33 and -6.49 as against standard pure Ibandronate of -1.28, -2.07, -1.97 and -3.23 kcal/mol. Also, ΔG binding energy and pIC50 values showed promising potential anti-osteoporotic effect for Ibandronate-hydroxyapatite conjugate.