A new sulfoxide analog of 1,2,3,6-tetrahydrophenylpyridine and antimicrobial activity

Bioactivities of thiotetrahydropyridines were previously described. Herein, a novel bioactive sulfoxide analog; N-acetyl-2-(1-adamantylsulfoxo)-3-acetoxy-4-phenyl-6-hydroxy-1,2,3,6-tetrahydropyridine (3) from the deoxydative substitution of 4-phenylpyridine 1-oxide is reported. Its structure was elucidated using spectral data including 2D-NMR, MS, IR and UV. The sulfoxide 3 exhibited antibacterial activity against Moraxella catarrhalis and Streptococcus pyogenes with minimum inhibitory concentration of 128 and 256 μg/mL, respectively

Investigation on biological activities of anthranilic acid sulfonamide analogs

In the previous studies, the cytotoxicities of anthranilate sulfonamides were investigated. Herein, the bioactivities of 4-substituted (X = NO2, OCH3, CH3, Cl) benzenesulfonamides of anthranilic acid (5-8) are reported. The results revealed that all sulfonamides selectively exerted antifungal activity (25-50 % inhibition) against C. albicans at 4 μg/mL. Furthermore, compounds 6 and 8 show antioxidative (SOD) activity. These sulfonamides, except for 6, selectively display cytotoxic effects toward MOLT-3 cells. It is interesting to note that sulfonamides with electron withdrawing substituent (5, X = NO2) exhibited the highest cytotoxicity. This study provided preliminary structure-activity relationship of the anthranilic sulfonamides that is useful for further in-depth investigation

Aromatase inhibitory activity of 1,4-naphthoquinone derivatives and QSAR study

A series of 2-amino(chloro)-3-chloro-1,4-naphthoquinone derivatives (1-11) were investigated for their aromatase inhibitory activities. 1,4-Naphthoquinones 1 and 4 were found to be the most potent compounds affording IC50 values 5.2 times lower than the reference drug, ketoconazole. A quantitative structure-activity relationship (QSAR) model provided good predictive performance (R2 CV = 0.9783 and RMSECV = 0.0748) and indicated mass (Mor04m and H8m), electronegativity (Mor08e), van der Waals volume (G1v) and structural information content index (SIC2) descriptors as key descriptors governing the activity. To investigate the effects of structural modifications on aromatase inhibitory activity, the model was employed to predict the activities of an additional set of 39 structurally modified compounds constructed in silico. The prediction suggested that the 2,3-disubstitution of 1,4-naphthoquinone ring with halogen atoms (i.e., Br, I and F) is the most effective modification for potent activity (1a, 1b and 1c). Importantly, compound 1b was predicted to be more potent than its parent compound 1 (11.90-fold) and the reference drug, letrozole (1.03-fold). The study suggests the 1,4-naphthoquinone derivatives as promising compounds to be further developed as a novel class of aromatase inhibitors

ANTIMICROBIAL, ANTIOXIDANT AND ANTICANCER ACTIVITIES OF STRYCHNOS LUCIDA R. BR.

Backgroud: Strychnos lucida R. Br. (Loganiaceae), a well-known indigenous medicine in Timor Leste, has been used for the treatment of ailments such as malaria, diarrhoea, fever, hypertension, cancer, diabetes mellitus and skin infections. Its pharmacological activity has never been reported. The aim of this study was to determine the biological activities of S. lucida, including antimicrobial, antioxidant and anticancer activities. Materials and methods: The stem, stem bark, twig and leaves of S. lucida were extracted by non-polar (hexane) and polar (ethyl acetate and methanol) solvents. Antimicrobial activity of the plant extracts against 29 microorganisms was evaluated using the agar dilution method and antioxidant properties were determined using DPPH and SOD assays. Anticancer activity was investigated against HepG2, HuCCA-1, A549 and MOLT-3 cell lines using the MTT and XTT assays. Results: It was found that the hexane and ethyl acetate extracts of S. lucida selectively inhibited the growth of Gram positive bacteria (Bacillus subtilis ATCC 6633, Bacillus cereus and Streptococcus pyogenes) with MICs range of 32-128 g/mL. Antioxidant activities, radical and superoxide scavenging properties, were observed for ethyl acetate and methanol extracts of S. lucida. Particularly, the ethyl acetate extracts selectively showed inhibitory activity against MOLT-3 cells. Notably, the plant extracts showed the relationship between antimicrobial, antioxidant and anticancer activities. Conclusion: The findings support the medicinal usage of S. lucida

Synthesis, Cytotoxic and Antimalarial Activities of Benzoyl Thiosemicarbazone Analogs of Isoquinoline and Related Compounds

Thiosemicarbazone analogs of papaveraldine and related compounds 1–6 were synthesized and evaluated for cytotoxic and antimalarial activities. The cytotoxic activity was tested against HuCCA-1, HepG2, A549 and MOLT-3 human cancer cell lines. Thiosemicarbazones 1–5 displayed cytotoxicity toward all the tested cell lines, while compounds 2–5 selectively showed potent activity against the MOLT-3 cell lines. Significantly, N(4)-phenyl-2-benzoylpyridine thiosemicarbazone 4 exhibited the most potent activity against HuCCA-1, HepG2, A549 and MOLT-3 cell lines with IC50 values of 0.03, 4.75, 0.04 and 0.004 µg/mL, respectively. In addition, 2-benzoylpyridine thio-semicarbazones 3 and 4 showed antimalarial activity against Plasmodium falciparum with IC50 of 10-7 to < 10-6 M. The study demonstrates the quite promising activity of analog 4 as a lead molecule for further development

Beta-(1-adamantylthio)pyridine analogs as antimicrobials and antimalarials

An array of interesting activities for bioactive 3-substituted thiopyridines have previously been reported. Herein, a series of α- and β-(1-adamantylthio) analogs of 3-picoline and phenylpyridines were prepared and investigated for antimicrobial (agar dilution method against 21 strains of microorganisms) and antimalarial (against P. falciparum) activities. It was found that β-thiopyridines, 5-(1-adamantylthio)-3-picoline (7) and 3-(1-adamantylthio)-4-phenylpyridine (8) are novel antimicrobials and antimalarials. Significantly, analogs 7 and 8 are very potent antimicrobials with MIC range of 2-32 µg/mL where 8 being the most potent. The β-sulfides 7 and 8 selectively inhibited the growth of tested gram-positive bacteria, but inactive against gram-negative bacilli including the members of Enterobacteriaceae. This study identified new antimicrobials that represent promising lead compounds suitable for fur-ther preclinical and clinical development

Synthesis of N-Substituted 5-Iodouracils as Antimicrobial and Anticancer Agents

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