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

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 H 37 Rv 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 (IC 50 ∼5±1 µg/ mL) and the other compound was shown closer activity (IC 50 ∼10±2µg/mL) compared with a methotrexate (IC 50 ∼5±1 µg/mL). The spectral studies (FT-IR, Mass, 1 HNMR and 13 CNMR) 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.

Novel Pyrimidine Derivatives from 2,5-Dichloro-3-acetylthienyl Chalcones as Antifungal, Antitubercular and Cytotoxic Agents: Design, Synthesis, Biological Activity and Docking Study

“…In our proposed investigation, it was extended to synthesize some novel pyrimidines from 2,5-dichloro-3-acetylthienyl chalcones, which has highly reactive dielectrophilic ketovinyl side chain to condense with guanidine hydrochloride in presence of KOH to produce twenty novel pyrimidine derivatives (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20) at room temperature and refluxed for 6 h (Scheme-I). The spectral characterizations were carried out on the synthesized pyrimidine derivatives using suitable IR, 1 H NMR, 13 C NMR, mass spectra and elemental analysis data.…”

“…All novel pyrimidine derivatives (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20) were exhibited characteristic absorption bands in the IR spectra (cm -1 ) in between 3400-3300 for amino-(-NH 2 ), 1650-1600 (C=N of pyrimidine), 1580-1560 (C=C) and at other regions of the spectrum depending upon the specific substituents present in each compound. 1 H NMR spectra of the aminopyrimidines was shown characteristic resonance signal for amino protons between δ 5.0-5.5 ppm.…”

“…Antitubercular activity: Antitubercular activity of all pyrimidines derivatives (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20) was conducted against M. tuberculosis H37Rv strain by broth dilution assay [19][20][21][22]. Among all pyrimidines derivatives, the compound 5 containing 2",4"dichlorophenyl moiety was shown 50 % activity (MIC = 6.2 µg/mL) compared to pyrazinamide (MIC = 3.12 µg/mL), whereas compounds 9 (MIC = 12.5 µg/mL) and 11 (MIC = 12.5 µg/mL) were exhibited 50 % activity compared to compound 5.…”

“…The synthesis of novel 2,5-dichloro-3-acetyl thienyl chalcone derivatives were reported in our recent studies. The resultant thienyl chalcone derivatives have exhibited potential antifungal, antitubercular and antiprostate cancer activities [16].…”

Molecular dynamics simulation approach of hybrid chalcone–thiazole complex derivatives for DNA gyrase B inhibition: lead generation

“…A wide range of bioactivities, including anticancer, 5–19 antitubercular, 20–31 antifungal, 32–39 antioxidant 40–45 and antibacterial, 46–54 are present in thiazole and chalcone derivatives. The degree of a particular biological activity is determined by the type of aryl ring attached to the chalcone and the variety of substituents on the thiazole ring.…”