Induced osteoblast differentiation by amide derivatives of stilbene: The possible osteogenic agents

Mohd Imran Ahamad; Ravi Prakash; Aijaz A John; Zahoor Wani; Deepika Yadav; Dnyaneshwar U Bawankule; Suaib Luqman; Feroz Khan; Divya Singh; Atul Gupta

doi:10.1016/j.bmcl.2020.127138

Induced osteoblast differentiation by amide derivatives of stilbene: The possible osteogenic agents

Bioorg Med Chem Lett. 2020 Jun 1;30(11):127138. doi: 10.1016/j.bmcl.2020.127138. Epub 2020 Mar 25.

Authors

Affiliations

¹ Medicinal Chemistry Department, CSIR-Central Institute of Medicinal and Aromatic Plants, P.O. CIMAP, Kukrail Road, Lucknow 226015, India.
² Division of Endocrinology, CSIR-Central Drug Research Institute, Sector-10, Jankipuram Extension, Lucknow 226 031, India.
³ Molecular Bioprospection Department, CSIR-Central Institute of Medicinal and Aromatic Plants, P.O. CIMAP, Kukrail Road, Lucknow 226015, India.
⁴ Metabolic and Structural Biology Department, CSIR-Central Institute of Medicinal and Aromatic Plants, P.O. CIMAP, Kukrail Road, Lucknow 226015, India.
⁵ Molecular Bioprospection Department, CSIR-Central Institute of Medicinal and Aromatic Plants, P.O. CIMAP, Kukrail Road, Lucknow 226015, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, Uttar Pradesh, 201002, India.
⁶ Metabolic and Structural Biology Department, CSIR-Central Institute of Medicinal and Aromatic Plants, P.O. CIMAP, Kukrail Road, Lucknow 226015, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, Uttar Pradesh, 201002, India.
⁷ Division of Endocrinology, CSIR-Central Drug Research Institute, Sector-10, Jankipuram Extension, Lucknow 226 031, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, Uttar Pradesh, 201002, India.
⁸ Medicinal Chemistry Department, CSIR-Central Institute of Medicinal and Aromatic Plants, P.O. CIMAP, Kukrail Road, Lucknow 226015, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, Uttar Pradesh, 201002, India. Electronic address: atisky2001@yahoo.co.in.

PMID: 32247734
DOI: 10.1016/j.bmcl.2020.127138

Abstract

A series of amide derivatives of stilbene was synthesized and investigated for osteogenic activity. Out of sixteen, seven compounds viz19c, 19g, 19i, 24b, 25a, 25c and 26a showed significant osteoblast differentiation within 1 pM-1 µM concentrations. Amongst all, 26a was identified as most active molecule which presented effective mineralization of osteoblasts and expression of mRNA of osteogenic marker gene such as BMP-2, ALP, and Runx-2 at 1 pM. In estrogen-deficient balb/c mice, 26a showed significant osteogenic activity at 5 mg-kg^-1 body weight dose. The protein expression study for estrogen receptors α and β (ER-α & ER-β) using mouse calvarial osteoblasts (MCOs) and molecular docking analyses showed preferential expression of ER-β by 26a indicating the possibility of ER-β mediated osteogenic activity of 26a.

Keywords: Anticancer; Bone-anabolic agents; Estrogen; Osteoporosis; Pterostilbene; Stilbene.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amides / chemistry*
Animals
Binding Sites
Bone Morphogenetic Protein 2 / genetics
Bone Morphogenetic Protein 2 / metabolism
Cell Differentiation / drug effects
Cell Survival / drug effects
Core Binding Factor Alpha 1 Subunit / genetics
Core Binding Factor Alpha 1 Subunit / metabolism
Estrogen Receptor alpha / genetics
Estrogen Receptor alpha / metabolism
Estrogen Receptor beta / chemistry
Estrogen Receptor beta / genetics
Estrogen Receptor beta / metabolism
Humans
MCF-7 Cells
Mice
Mice, Inbred BALB C
Molecular Docking Simulation
Osteoblasts / cytology
Osteoblasts / metabolism
Osteogenesis / drug effects
RNA, Messenger / metabolism
Raloxifene Hydrochloride / chemistry
Raloxifene Hydrochloride / metabolism
Raloxifene Hydrochloride / pharmacology
Stilbenes / chemistry*
Stilbenes / metabolism
Stilbenes / pharmacology

Substances

Amides
Bone Morphogenetic Protein 2
Core Binding Factor Alpha 1 Subunit
Estrogen Receptor alpha
Estrogen Receptor beta
RNA, Messenger
Runx2 protein, mouse
Stilbenes
Raloxifene Hydrochloride