Modular Synthesis and Antiproliferative Activity of New Dihydro-1H-pyrazolo[1,3-b]pyridine Embelin Derivatives.

Pedro Martín-Acosta,Ana Estévez-Braun,Miguel Guerra-Rodríguez,Ángel Amesty,Leandro Fernández-Pérez,Borja Guerra

doi:10.3390/ph14101026

Abstract

A set of new dihydro-1H-pyrazolo[1,3-b]pyridine and pyrazolo[1,3-b]pyridine embelin derivatives was synthesized through a multicomponent reaction from natural embelin, 3-substituted-5-aminopyrazoles and aldehydes. The synthesized compounds were evaluated against three hematologic tumor cell lines, HEL (acute erythroid leukemia), K-562 (chronic myeloid leukemia) and HL-60 (acute myeloid leukemia), and five breast cancer cell lines (SKBR3, MCF-7, MDA-MB-231, BT-549, HS-578T). The primate non-malignant kidney Vero cell line was used as the control of cytotoxicity. From the obtained results, some structure–activity relationships were outlined. Furthermore, in silico prediction of physicochemical properties and ADME parameters were determined for the derivatives with the best antiproliferative values.

Highlights

Heterocyclic compounds are of great importance in medicinal chemistry [1]
Titarenko et al demonstrated during the development of the BioCore strategy [3] that more than 67% of the molecules included in the “Comprehensive Medicinal Chemistry” database contain heterocyclic rings
%)preparation was used an derivatives from the natural benzoquinone embelin

Summary

Introduction

Heterocyclic compounds are of great importance in medicinal chemistry [1]. Molecules with these structures are present in many essential compounds for life as nucleic acids, amino acids, chlorophyll or vitamins, among others [2]. Titarenko et al demonstrated during the development of the BioCore strategy [3] that more than 67% of the molecules included in the “Comprehensive Medicinal Chemistry” database contain heterocyclic rings. The combination of both is frequently present in alkaloids and drugs [5]. Among all heterocycles, nitrogenated heterocycles are relevant in medicinal chemistry. An analysis of the approved drugs by the FDA database conducted by Njardarson et al [6], revealed that 59% of them contained nitrogenated heterocycles

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Results

Conclusion