Novel Biginelli dihydropyrimidines with potential anticancer activity: a parallel synthesis and CoMSIA study

Area of Science:

• Medicinal Chemistry
• Organic Synthesis
• Pharmacology

Background:

• Biginelli dihydropyrimidines are heterocyclic compounds with diverse biological activities.
• Exploring novel dihydropyrimidines is crucial for identifying new therapeutic agents.
• The MCF-7 human breast cancer cell line is a standard model for evaluating anticancer drug efficacy.

Purpose of the Study:

• To synthesize novel Biginelli dihydropyrimidines using p-toluene sulphonic acid as a catalyst.
• To evaluate the in vitro antioxidant activity of the synthesized compounds using the DPPH method.
• To assess the in vitro anticancer activity of the synthesized compounds against MCF-7 human breast cancer cells and elucidate structure-activity relationships.

Main Methods:

• Synthesis of 32 novel Biginelli dihydropyrimidines.
• In vitro antioxidant activity assessment using the DPPH assay.
• In vitro anticancer activity evaluation against MCF-7 cells at 10 microg concentration.
• Comparative molecular similarity indices analysis (CoMSIA) for 3D QSAR.

Main Results:

• Compounds 28 and 29 demonstrated notable in vitro antioxidant activity.
• Compounds 10 and 11 exhibited significant in vitro anticancer activity against MCF-7 cells, with varying cytotoxicity percentages.
• 3D QSAR analysis provided insights into structure-activity relationships for anticancer effects.

Conclusions:

• The study successfully synthesized and characterized novel Biginelli dihydropyrimidines.
• Specific compounds displayed promising antioxidant and anticancer properties, warranting further investigation.
• The 3D QSAR analysis aids in understanding the structural basis for the observed anticancer activity.