Synthesis and evaluation of thiazolidinone-pyrazole conjugates as anticancer and antimicrobial agents

Mahima Bhat; Boja Poojary; Bhuvanesh Sukhlal Kalal; Purawarga Matada Gurubasavaraja Swamy; Senthamaraikannan Kabilan; Vasantha Kumar; Nooji Shruthi; Selvam Athavan Alias Anand; Vinitha Ramanath Pai

doi:10.4155/fmc-2017-0191

Synthesis and evaluation of thiazolidinone-pyrazole conjugates as anticancer and antimicrobial agents

Future Med Chem. 2018 May 1;10(9):1017-1036. doi: 10.4155/fmc-2017-0191. Epub 2018 Apr 30.

Authors

Mahima Bhat¹, Boja Poojary¹, Bhuvanesh Sukhlal Kalal^{2

3}, Purawarga Matada Gurubasavaraja Swamy⁴, Senthamaraikannan Kabilan⁵, Vasantha Kumar⁶, Nooji Shruthi¹, Selvam Athavan Alias Anand⁵, Vinitha Ramanath Pai²

Affiliations

¹ Department of Chemistry, Mangalore University, Mangalagangothri-574199, Karnataka, India.
² Department of Biochemistry, Yenepoya Medical College, Yenepoya University, Mangaluru, Karnataka, India.
³ Yenepoya Research Center, Yenepoya University, Mangaluru, Karnataka, India.
⁴ Medicinal Chemistry Research Laboratory, Acharya & BM Reddy College of Pharmacy, Bangalore 560090, Karnataka, India.
⁵ Drug Discovery Lab, Department of Chemistry, Annamalai University, Annamalainagar, Tamil Nadu 608002, India.
⁶ Department of Chemistry, SDM College (Autonomous), Ujire-574240, Karnataka, India.

PMID: 29708431
DOI: 10.4155/fmc-2017-0191

Abstract

Aim: To synthesize a series of new thiazolidinone-pyrazole hybrids (5a-o) and assess their anticancer (in vitro and in vivo) and antimicrobial activities.

Results: The compounds 5h (against Ehrlich ascites carcinoma cells), 5e and 5i (against the human breast cancer [MDA-MB231] cell line) exhibited potent anticancer activity. All the compounds except 5g and 5e found to be less toxic for the human dermal fibroblast cells. The effective interactions of the compounds in silico with MDM2 exemplified their inhibitory potency. The derivatives also showed moderate antimicrobial activity.

Conclusion: The halogen atoms on various positions of the N-arylamino ring played an advantageous role in elevating the potency of the molecules. Thus, these conjugates could be used as a lead for further optimization to achieve promising therapeutics.

Keywords: A375; ADME parameters; HDF; MDA-MB-231; MDM2; N-arylpyrazole; anticancer activity; cytotoxicity; molecular docking; molecular dynamics simulation; p53; thiazolidin-4-one.

Publication types

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

MeSH terms

Animals
Anti-Infective Agents / chemical synthesis
Anti-Infective Agents / chemistry*
Anti-Infective Agents / pharmacology
Anti-Infective Agents / therapeutic use
Antineoplastic Agents / chemical synthesis
Antineoplastic Agents / chemistry*
Antineoplastic Agents / pharmacology
Antineoplastic Agents / therapeutic use
Bacteria / drug effects
Bacterial Infections / drug therapy
Candida albicans / drug effects
Candidiasis / drug therapy
Cell Line, Tumor
Cell Survival / drug effects
Humans
Mice
Molecular Docking Simulation
Neoplasms / drug therapy
Neoplasms / metabolism
Proto-Oncogene Proteins c-mdm2 / metabolism
Pyrazoles / chemical synthesis
Pyrazoles / chemistry*
Pyrazoles / pharmacology
Pyrazoles / therapeutic use
Structure-Activity Relationship
Thiazolidines / chemical synthesis
Thiazolidines / chemistry*
Thiazolidines / pharmacology
Thiazolidines / therapeutic use

Substances

4-thiazolidinone
Anti-Infective Agents
Antineoplastic Agents
Pyrazoles
Thiazolidines
Proto-Oncogene Proteins c-mdm2