New gem-dichlorocyclopropane-pyrazole hybrids with monoterpenic skeleton: Synthesis, crystal structure, cytotoxic evaluation, molecular dynamics and theoretical study

A new series of four gem-dichlorocyclopropane-pyrazole hybrids 3a-d have been synthesized from (R)-carvone, using a two-step procedure consisting of dichlorocyclopropanation under phase transfer catalysis conditions followed by a 1,3-dipolar cycloaddition reaction of the obtained cyclopropanic product with diarylnitrilimines. The structure of the target products 3a-d was fully established via spectroscopic analysis (H-1- & C-13 NMR and HRMS) as well as an X-ray crystallographic study carried out on compound 3d An attempt to prepare the corresponding thiosemicarbazones was unsuccessful. So, a succinct theoretical study was carried out to explain the non-reactivity of the hybrids 3a-d vis a vis thiosemicarbazide. Furthermore, all the compunds were evaluated for their anticancer activity against HT-1080 fibrosarcoma, breast adenocarcinoma (MCF-7 and MDA-MB231), and lung carcinoma A-549 cells. The four newly synthesized compounds ( 3a-d ) exhibited interesting antiproliferative activities with IC50 values ranging from 25.78 +/- 0.24 mu M to 37.13 +/- 0.47 mu M. Molecular docking and molecular dynamics confirmed the empirical test results and confirmed the stability of the complex during inhibition of the anti-apoptotic protein for killing cancer cells. (C) 2022 Elsevier B.V. All rights reserved.

Automated summary

A series of gem-dichlorocyclopropane-pyrazole hybrids were synthesized and their structure and anticancer activity were investigated. The synthesized compounds exhibited interesting antiproliferative activities.