Pyrazoline analogues: Design, synthesis, and evaluation of anti-osteoporosis activity

Kriti Sharma; Ashok Kumar; Ravi Prakash; Alok Tripathi; Rohit Singh; Ranju Bajpai; Amogh A Sahasrabuddhe; Divya Singh; T Narender

doi:10.1016/j.bmcl.2022.128585

Pyrazoline analogues: Design, synthesis, and evaluation of anti-osteoporosis activity

Bioorg Med Chem Lett. 2022 Mar 15:60:128585. doi: 10.1016/j.bmcl.2022.128585. Epub 2022 Jan 25.

Authors

Kriti Sharma¹, Ashok Kumar², Ravi Prakash³, Alok Tripathi¹, Rohit Singh⁴, Ranju Bajpai⁵, Amogh A Sahasrabuddhe⁵, Divya Singh⁶, T Narender⁷

Affiliations

¹ Division of Endocrinology, CSIR-Central Drug Research Institute, Lucknow 226031, Uttar Pradesh, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, Uttar Pradesh 201002, India.
² Division of Medicinal and Process Chemistry, CSIR-Central Drug Research Institute, Lucknow 226031, Uttar Pradesh, India.
³ Division of Endocrinology, CSIR-Central Drug Research Institute, Lucknow 226031, Uttar Pradesh, India.
⁴ Division of Medicinal and Process Chemistry, CSIR-Central Drug Research Institute, Lucknow 226031, Uttar Pradesh, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, Uttar Pradesh 201002, India.
⁵ Biochemistry and Structural Biology Division, CSIR-Central Drug Research Institute, Lucknow 226031, Uttar Pradesh, India.
⁶ Division of Endocrinology, CSIR-Central Drug Research Institute, Lucknow 226031, Uttar Pradesh, India. Electronic address: [email protected].
⁷ Division of Medicinal and Process Chemistry, CSIR-Central Drug Research Institute, Lucknow 226031, Uttar Pradesh, India. Electronic address: [email protected].

PMID: 35085723
DOI: 10.1016/j.bmcl.2022.128585

Abstract

A series of pyrazoline compounds were synthesised and their osteogenic potential was explored. Out of fifteen, six compounds (3a, 4ac, 5aaa, 7, 8ab and 4aa) showed significant osteoblast differentiation in the range of 1 pM -1 μM concentrations. Amongst all, compound 4aa was identified as most active molecule which showed effective mineralisation of osteoblast cells and up regulates the osteogenic marker gene such as Bmp-2, Runx-2 and Type-1col at both transcriptional and translational level. Besides exhibiting potential osteogenic activity, 4aa also possess significant anti-apoptotic activity at 1 pM &100 pM concentration and increases the osteoblast survival in serum deprived conditions.

Keywords: Cell viability; Mineralisation; Osteoblast apoptosis; Osteoblast differentiation.

Publication types

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

MeSH terms

Apoptosis / drug effects
Bone Morphogenetic Protein 2 / genetics
Bone Morphogenetic Protein 2 / metabolism
Cell Differentiation / drug effects
Core Binding Factor Alpha 1 Subunit / genetics
Core Binding Factor Alpha 1 Subunit / metabolism
Dose-Response Relationship, Drug
Drug Design*
Humans
Molecular Structure
Osteoblasts / drug effects
Osteogenesis / drug effects*
Pyrazoles / chemical synthesis
Pyrazoles / chemistry
Pyrazoles / pharmacology*
Structure-Activity Relationship

Substances

BMP2 protein, human
Bone Morphogenetic Protein 2
Core Binding Factor Alpha 1 Subunit
Pyrazoles
RUNX2 protein, human