Synthesis and biological evaluation of purine-pyrazole hybrids incorporating thiazole, thiazolidinone or rhodanine moiety as 15-LOX inhibitors endowed with anticancer and antioxidant potential
| Autor: | Marwa M. Abu-Serie, Alaa A. El-Tombary, S. A. Shams El-Dine, Heba A. Abd El Razik, Omaima G. Shaaban, Fawzia A. Ashour, Ola S. Afifi |
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| Rok vydání: | 2019 |
| Předmět: |
Antioxidant
Rhodanine DPPH medicine.medical_treatment Antineoplastic Agents Pyrazole 01 natural sciences Biochemistry Antioxidants Structure-Activity Relationship chemistry.chemical_compound Picrates Cell Line Tumor Drug Discovery medicine Arachidonate 15-Lipoxygenase Humans Structure–activity relationship Lipoxygenase Inhibitors Thiazole Molecular Biology Cell Proliferation Dose-Response Relationship Drug Molecular Structure 010405 organic chemistry Biphenyl Compounds Organic Chemistry Ascorbic acid 0104 chemical sciences Molecular Docking Simulation Thiazoles 010404 medicinal & biomolecular chemistry chemistry Purines Docking (molecular) Pyrazoles Thiazolidines Drug Screening Assays Antitumor |
| Zdroj: | Bioorganic Chemistry. 87:821-837 |
| ISSN: | 0045-2068 |
| Popis: | Novel purine-pyrazole hybrids combining thiazoles, thiazolidinones and rhodanines, were designed and tested as 15-LOX inhibitors, potential anticancer and antioxidant agents. All tested compounds were found to be potent 15-LOX inhibitors with IC50 ranging from 1.76 to 6.12 µM. The prepared compounds were evaluated in vitro against five cancer cell lines: A549 (lung), Caco-2 (colon), PC3 (prostate), MCF-7 (breast) and HepG-2 (liver). Compounds 7b and 8b displayed broad spectrum anticancer activity against the five tested cell lines (IC50 = 18.5–95.39 µM). While, compound 7h demonstrated moderate anticancer activity against lung A549 and colon Caco-2 cell lines. Antioxidant screening revealed that six compounds (5a, 5b, 6b, 7b, 7h and 8b) with IC50 ranging from 0.93 to 14.43 µg/ml were found to be more potent scavengers of 2,2- diphenyl-1-picrylhydrazyl (DPPH) than the reference ascorbic acid with IC50 value of 15.34 µg/ml. Compounds 7b, 7h and 8b, when evaluated for their antioxidant activity, where found to be potent DPPH scavengers. Moreover, compound 7b displayed twice the potency of ascorbic acid as NO scavenger. Docking study was performed to elucidate the possible binding mode of the most active compounds with the active site of 15-LOX enzyme. Collectively, the purine-pyrazole hybrids having thiazoline or thizolidinone moieties (7b, 7h and 8b) constitute a promising scaffold in designing more potent 15-LOX inhibitors with anticancer and antioxidant potential. |
| Databáze: | OpenAIRE |
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