SYNTHESIS AND BIOLOGICAL EVALUATION OF NOVEL PYRAZOLO[3,4-D]PYRIMIDINE DERIVATIVES OF EXPECTED ANTICANCER ACTIVITY

Mohamed Alswah

doi:10.21608/ajps.2021.187757

Abstract

A series of novel pyrazolo[3,4-d]pyrimidine derivatives have designed and synthesized in synthetically useful yields. All the new synthesized compounds were biologically evaluated in vitro for their cytotoxic activities against a panel of three cancer cell lines namely, HepG-2, MCF-7, and HCT-116. The results of cytotoxic evaluation indicated that compound (9) exhibited the most prominent cytotoxic effect against all tested cell lines with IC50 values ranging from (4.03- 6.18) µM comparable to that of doxorubicin as a control drug (IC50 values of 8.17 and 9.27 µM). In particular, compounds (8,9,11) and (12) exhibited higher intercalative activity with IC50 value of 30 µM than doxorubicin (31 µM).

Highlights

Cancer remains one of the most common causes of death throughout the world and the development of potent and more effective anticancer agents represents one of the most important challenges in therapeutics due to the unrivaled pathophysiology of tumors and the predictable emergence of resistance to medication (Thun et al 2010)
Anticancer drugs have been classified into two main target types: the first one is drugs that target DNA, RNA, or proteins
Chemistry: The designed compounds were synthesized as outlined in schemes 1 and 2

Summary

Introduction

Cancer remains one of the most common causes of death throughout the world and the development of potent and more effective anticancer agents represents one of the most important challenges in therapeutics due to the unrivaled pathophysiology of tumors and the predictable emergence of resistance to medication (Thun et al 2010). Another type of Topo II-targeting drugs, including intercalating drugs, interfere with the enzyme’s cleavage and rejoining activities by trapping the cleavable complex and thereby increasing the time of the transient Topo II-catalyzed DNA breaks.

Results

Conclusion