Synthesis and Biological Activity of Novel 2,5-Dichloro-3-Acetylthiophene Chalcone Derivatives

Abstract

Abstract: Objective: A series of novel 2, 5-dichloro-3-acetylthiophene chalcone derivatives were synthesized by Claisen-Schmidt condensation and evaluated for them in vitro antifungal, antitubercular activities and cytotoxic activity against DU145 (prostate) cancer cell line. Methods: Among all series of synthesized compounds, four compounds were displayed proximity of antifungal activity (MIC ≤ 8.0 μg/mL) towards the fungus species Aspergillus niger (ATCC 6275, An) and Candida tropicalis (ATCC 1369, Ct) and compared against fluconazole standard (MIC ≤ 1.0 μg/mL) by agar-diffusion and tube dilution methods. Results: One compound was shown a promising antimycobacterial activity (MIC∼3.12 μg/mL) correlated with pyrazinamide (MIC∼3.12 μg/mL) and also another five compounds exhibited better activity (MIC∼6.25 μg/mL) towards M. tuberculosis H37Rv species. All series of compounds were treated with DU145 cells and tested for cytotoxicity by MTT assay. Among all, one compound was shown similar cytotoxicity activity (IC50 ∼5±1 μg/ mL) and the other compound was shown closer activity (IC50∼10±2μg/mL) compared with a methotrexate (IC50 ∼5±1 μg/mL). The spectral studies (FT-IR, Mass, 1HNMR and 13CNMR) studies provided new molecular scaffolds with detailed structure-activity relationship. Conclusion: These novel chalcones with thienyl ring structure would be promising new scaffold for establishing specific targets on fungal, mycobacteria species and other cancer cell lines. Key words: 2, 5-Dichloro-3-acetylthiophene chalcone derivatives, Claisen-Schmidt condensation, Cytotoxic activity, DU145 (prostate) cancer cell line, Structure-activity relationship, Antifungal activity, Antitubercular activity.