Design, Facile Synthesis and Characterization of Dichloro Substituted Chalcones and Dihydropyrazole Derivatives for Their Antifungal, Antitubercular and Antiproliferative Activities

Infectious diseases caused by fungi and mycobacteria pose an important problem for humankind. Similarly, cancer is one of the leading causes of death globally. Therefore, there is an urgent need for the development of novel agents to combat the deadly problems of cancer, tuberculosis, and also fungal infections. Hence, in the present study, we designed, synthesized, and characterized 30 compounds including 15 chalcones (2–16) and 15 dihydropyrazoles (17–31) containing dichlorophenyl moiety and also screened these compounds for their antifungal, antitubercular, and antiproliferative activities. Among these compounds, the dihydropyrazoles showed excellent antifungal and antitubercular activities whereas the chalcones exhibited promising antiproliferative activity. Among the dihydropyrazoles, compound 31 containing 2-thienyl moiety showed promising antifungal activity (MIC 5.35 µM), whereas compounds 22 and 24 containing 2,4-difluorophenyl and 4-trifluoromethyl scaffolds revealed significant antitubercular activity with the MICs of 3.96 and 3.67 µM, respectively. Compound 16 containing 2-thienyl moiety in the chalcone series showed the highest anti-proliferative activity with an IC₅₀ value of 17 ± 1 µM. The most active compounds identified through this study could be considered as starting points in the development of drugs with potential antifungal, antitubercular, and antiproliferative activities

Synthesis, and biological screening of chloropyrazine conjugated benzothiazepine derivatives as potential antimicrobial, antitubercular and cytotoxic agents

A series of twenty new chloropyrazine conjugated benzothiazepines (22-41) have been synthesized with 58%–95% yields. The compounds were characterized by using different spectroscopic techniques including FT-IR, ¹H NMR, ¹³C NMR spectroscopy and mass spectrometry. The synthesized compounds (22-41) and their precursor chalcones (2-21) were evaluated for antitubercular and cytotoxic activities. Additionally, compounds 22-41 were also tested for antimicrobial activity. Among the chalcone series (2-21), compounds 7 and 14 showed significant antitubercular activities (MICs 25.51 and 23.89 µM, respectively), whereas among benzothiazepines (22-41), compounds 27 and 34 displayed significant antimicrobial (MICs 38.02 µM, 19.01 µM) and antitubercular (MIC 18.10 µM) activities. Compounds 7 and 41 displayed cytotoxic activities with IC₅₀ of 46.03 ± 1 and 35.10 ± 2 µM respectively. All the compounds were evaluated for cytotoxic activity on normal human liver cell lines (L02) and found to be relatively less selective towards this cell line. The most active compounds identified through this study could be considered as potential leads for the development of drugs with possible antimicrobial, antitubercular, and cytotoxic activities

Antitubercular activity assessment of fluorinated chalcones, 2-aminopyridine-3-carbonitrile and 2-amino-4H-pyran-3-carbonitrile derivatives: In vitro, molecular docking and in-silico drug likeliness studies

A series of newer previously synthesized fluorinated chalcones and their 2-amino-pyridine-3-carbonitrile and 2-amino-4H-pyran-3-carbonitrile derivatives were screened for their in vitro antitubercular activity and in silico methods. Compound 40 (MIC~ 8 μM) was the most potent among all 60 compounds, whose potency is comparable with broad spectrum antibiotics like ciprofloxacin and streptomycin and three times more potent than pyrazinamide. Additionally, compound 40 was also less selective and hence non-toxic towards the human live cell lines-LO2 in its MTT assay. Compounds 30, 27, 50, 41, 51, and 60 have exhibited streptomycin like activity (MIC~16–18 μM). Fluorinated chalcones, pyridine and pyran derivatives were found to occupy prime position in thymidylate kinase enzymatic pockets in molecular docking studies. The molecule 40 being most potent had shown a binding energy of -9.67 Kcal/mol, while docking against thymidylate kinase, which was compared with its in vitro MIC value (~8 μM). These findings suggest that 2-aminopyridine-3-carbonitrile and 2-amino-4H-pyran-3-carbonitrile derivatives are prospective lead molecules for the development of novel antitubercular drugs

In vitro Antimicrobial activity of Acacia nilotica, Ziziphus mauritiana, Bauhinia variegate and Lantana camara against some clinical isolated strains

Abstract Plants are potent biochemists; biologically active compounds present in the medicinal plants have always been of great interest to scientists working in this field. Thus, the aim of the current study was to screen the antimicrobial activity of Acacia nilotica, Ziziphus mauritiana, Bauhinia variegate and Lantana camara against some selected clinical isolated strains. Although previous studies have documented the antimicrobial properties of these plants, this work is designed to evaluate the specific antibacterial activity of different extracts of these plants against tested microorganisms, in order to know the best extract against specific microorganisms. In this study the fresh parts (leaves, barks & pods) of the test medicinal plant were collected and methanol, ethanol and ethyl acetate extracts were prepared. Antibacterial susceptibility test was done by using Agar diffusion assay method. Statistical analysis was carried out with SPSS 17.0 Windows version. The results of the current study showed that a total of 8 extracts from 4 different plant species were investigated including pods of ethyl acetate extracts of Lantana camara, which showed the highest antimicrobial activity against tested clinical isolates (Bacillus subtilus 2±0.1mm, Bacillus circulans 2.6±0.2mm, Bacillus sphaericius 2±0.1mm, Staphylococcus aureus 2.5±0.1, and Serratia liquefaciens 2.2±0.1mm), followed by its ethyl acetate extracts of leaves. Bark extracts of four tested medicinal plants possess a lower zone on inhibitory activity as compared to the leaves extracts of these plants. Noticeably no antimicrobial activity was found in the methonolic bark extract of Acacia nilotica against the tested bacteria except Bacillu ciurlans. The results of the present investigation clearly indicate that the antibacterial activity varies with the species of the plants and plant material used. Thus, the study ascertains the value of plants used in ayurveda, which could be of considerable interest to the development of new drugs. Studies are in progress to further evaluate the mechanisms of action of these active test extracts on study organisms associated with certain human diseases