Synthesis, thymidine phosphorylase, angiogenic inhibition and molecular docking study of isoquinoline derivatives

• Published in: Bioorganic Chemistry
• Main Author: Zaman K.; Rahim F.; Taha M.; Wadood A.; Adnan Ali Shah S.; Gollapalli M.; Ullah F.; Ahmed A.
• Format: Article
• Language: English
• Published: Academic Press Inc. 2019
• Online Access: https://www.scopus.com/inward/record.uri?eid=2-s2.0-85066282970&doi=10.1016%2fj.bioorg.2019.102999&partnerID=40&md5=b49a72ea77f2bff64cf00a1aaf278f15

Isoquinoline analogues (KA-1 to 16) have been synthesized and evaluated for their E. coli thymidine phosphorylase inhibitory activity. Except compound 11, all other analogs showed outstanding thymidine inhibitory potential ranging in between 4.40 ± 0.20 to 69.30 ± 1.80 µM when compared with standard drug 7-Deazaxanthine (IC50 = 38.68 ± 4.42 µM). Structure Activity Relationships has been established for all compounds, mainly based on substitution pattern on phenyl ring. All analogs were characterized by various spectroscopic techniques such as 1H NMR, 13C NMR and EI-MS. The binding interactions of isoquinoline analogues with the active site of TP enzyme, the molecular docking studies were performed. Furthermore, the angiogenic inhibitory potentials of isoquinoline analogues (KA-1-9, 14, 12 and 16) were determined in the presence of standard drug Dexamethasone based on percentage inhibitions at various concentrations. Herein this work analogue KA-12, 14 and 16 emerged with most potent angiogenic inhibitory potentials among the synthesized analogues. © 2019 Elsevier Inc.