Fluoroquinolones as a potentially novel class of antidiabesity and antiproliferative compounds: synthesis and docking studies

Author:

Kasabri Violet1,Arabiyat Shereen12,Al-Hiari Yusuf1,Zalloum Hiba3,Almaliti Jehad1,Telfah Ahmad4,Bustanji Yasser K.3,Alalawi Sundus1

Affiliation:

1. School of Pharmacy, The University of Jordan, Queen Rania Street, Amman 11942, Jordan.

2. Salt College, Al-Balqa Applied University, Salt 19117, Jordan.

3. Hamdi Mango Research Centre for Scientific Research, The University of Jordan, Amman 11942, Jordan.

4. Leibniz Institut für analytische Wissenschaften – ISAS e.V. Bunsen-Kirchhoff-Str.1144139 Dortmund, Germany.

Abstract

Intense efforts by the pharmaceutical industry have been made to identify new targets for obesity diabetes (diabesity). Pancreatic triacylglycerol lipase (PL) inhibition is an interesting putative target for obesity management. Fluoroquinolones (FQs) have been identified as potent inhibitors of PL. The aim of this research was to synthesize novel FQs and evaluate their in vitro antilipolytic and antiproliferative properties. Characterization of the synthesized FQs was carried out with NMR, MS, IR, and EA. Like orlistat, potential FQs’ modulation of PL was quantified colorimetrically (n = 3) and was further supported by docking studies. Compared with cisplatin, FQs’ antiproliferative propensities against a panel of obesity related colorectal cancer cell lines were investigated with Sulforhodamine B assay. Twelve novel FQs (2A–5A, 2B–5B, and 2C–5C) were synthesized and characterized. The PL-IC50 values of tested FQs were in the range of 6.8–165.7 μmol/L. FQ 4A was the most active antiproliferative compound against HCT116 with an IC50 value of 3.5 μmol/L. Their selectivity of growth inhibition for safety examination using normal periodontal ligament fibroblasts (PDL) in comparison with cisplatin’s lack of differential cytotoxicity was reported. Lipophilicity and hydrogen bonding were found essential for both activities. Conclusively, FQs are robustly proven for their emerging in vitro anti-obesity and antiproliferative activities.

Publisher

Canadian Science Publishing

Subject

Organic Chemistry,General Chemistry,Catalysis

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