High therapeutic potential of Spilanthes acmella

Spilanthes acmella, a well known antitoothache plant with high medicinal usages, has been recognized as an important medicinal plant and has an increasingly high demand worldwide. From its traditional uses in health care and food, extensive phytochemical studies have been reported. This review provides an overview and general description of the plant species, bioactive metabolites and important pharmacological activities including the preparation, purification and in vitro large-scale production. Structure-activity relationships of the bioactive compounds have been discussed. Considering data from the literature, it could be demonstrated that S. acmella possesses diverse bioactive properties and immense utilization in medicine, health care, cosmetics and as health supplements. As a health food, it is enriched with high therapeutic value with high potential for further development

Novel activities of 1-adamantylthiopyridines as antibacterials, antimalarials and anticancers

To discover new bioactive lead compounds for medicinal purposes, herein, 2(1-adamantylthio)pyridine and derivatives (1-10) were prepared and tested for antibacterial (agar dilution method against 27 strains of microorganisms), antimalarial (against Plasmodium falciparum) and anticancer (MOLT-3, HepG2, HuCCA-1 and A549) activities. Results showed that all the tested derivatives selectively exerted antigrowth activity against Streptococci at 15-30 µg/mL. 3-Substituted (R) thiopyridines; 3 (R = NAc2), 5 (R = OH) and 6 (R = Br) exhibited antibacterials, antimalarials and anticancers. Significantly, 6-(1-adamantylthio) nicotinonitrile (10) is a promising antibacterial which selectively displays antigrowth activity against Vibrio cholerae, Vibrio parahaemolyticus, Edwardsiella tarda and beta-hemolytic Streptococcus group A with minimum inhibitory concentration of 30 µg/mL. The findings reveal that these 1-adamantylthiopyridines represent a novel class of antibacterial, antimalarial and anticancer agents with potential medicinal values

Anti-invasive effects of curcuminoid compounds from Curcuma aromatica Salisb. on murine colon 26-L5 carcinoma cells

ショウガ科に属する Curcuma aromatica Salisb. の根茎のクロロホルム抽出エキスから,化学構造の明らかな4種のクルクミンおよびその関連化合物:curcumin(CA-1),demethoxycurcumin(CA-2),5\u27-methoxycurcumin(CA-3),bisdemethoxycurcumin(CA-4)を分離した。これらの化合物を用いてマウス結腸癌細胞(colon 26-L5)に対する増殖,基底膜への浸潤,細胞運動に及ぼす効果について検討した。クルクミン(CA-1)とその関連化合物(CA-2,3 および4)は,細胞に対して傷害性を示さない10μMの濃度において,マウス結腸癌細胞の基底膜への浸潤を抑制した(それぞれ22.8,28.9,10.3および62.0%の抑制率)。この癌細胞の運動能に対しても同様の抑制効果が観察された。これらのクルクミン関連化合物の中で,CA-4は強い抑制活性を持ち,癌細胞の浸潤および運動能に対して濃度依存的な抑制効果を示した。このように,クルクミン関連化合物の芳香族環のhydroxyl基およびmethoxyl基が癌細胞の浸潤活性の発現と関係している可能性が示唆された。 Bioassay-directed fractionation of the active chloroform extract from the rhizomes of Curcuma aromatica Salisb. (Zingiberaceae) led to the isolation of four main curcuminoid constituents: curcumin (CA-1), demethoxycurcumin (CA-2), 5\u27-methoxycurcumin (CA-3) and bisdemethoxycurcumin (CA-4). This is the first report to describe the isolation of CA-3 from C. aromatica. The chemical structures of these compounds were determined on the basis of spectral analysis and their inhibitory effects on the proliferation, invasion and migration of murine colon 26-L5 adenocarcinoma cells were evaluated in vitro. Curcumin and its analogues (CA-2, 3 and 4), at the non-cytotoxic concentration of 10μM, inhibited the invasive ability of colon 26-L5 cells to the ranges of 22.8, 28.9, 10.3 and 62.0%, respectively. A similar effect of these constituents on the migration of colon 26-L5 cells was also observed. Among these curcuminoids, CA-4 showed the strongest activities, inhibiting both tumor cell invasion and migration in a concentration-dependent manner

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

Activities of thiotetrahydropyridines as antioxidant and antimicrobial agents

Tetrahydropyridines have been reported previously as important medicinal agents. The present study, thiotetrahydropyridines were prepared and tested for antioxidants (DPPH and SOD assays) and antimicrobials (agar dilution method). The results show that 1-acetyl-1,2,3,4- and 1,2,3,6-thiotetrahydropyridines 15a-b, 16, 17 and 18a are new antioxidants that scavenge superoxide and free radicals. Whereas the analogs 15a and 16 are novel antimicrobials. Significantly, 1-acetyl-2-(1-adamantylthio)-3,4-diacetoxy-1,2,3,4-tetrahydropyridine (15a) is the most potent compound that inhibits the growth of Streptococcus pyogenes and Moraxella catarrhalis with MIC of 32 µg/mL, of Corynebacterium diphtheriae NCTC 10356 and of Vibrio cholerae (MIC of 64 µg/mL). Remarkably, the analog 15a is the most potent antioxidant and antimicrobial agent. This finding reveals a new and unique group of 1-acetyl-1,2,3,4-thiotetrahydropyridines as interesting lead compound with potential to be further developed for medicinal applications

Antimicrobial and antioxidative activities of 1-adamantylthio derivatives of 3-substituted pyridines

Diverse biological activities of sulfur containing pyridines were reported. To investigate for new lead compounds, thus, 1-adamantylthiopyridines bearing 3-substituents (OEt, OAc, NAc2, Br and OH) were prepared and evaluated for antimicrobial and antioxidative activities. The antimicrobial assay against 27 strains of microorganisms was performed using agar dilution method. The results show that all the tested 2-(1-adamantylthio)-3-ethoxypyridine (4a), 2-(1-adamantylthio)-3-acetoxypyridine (4b), N-acetyl-2-(1-adamantylthio)-3-acetamidopyridine (4c), 2-(1-adamantylthio)-3-bromopyridine (4d), 2-(1-adamantylthio)-5-hydroxypyridine (5) and 3-(1-adamantylthio)-5-bromopyridine (6) exhibit antigrowth activity on Streptococci at 30 µg/mL. Particularly, the thiopyridines 4c, 5 and 6 are the most active compounds, displaying complete inhibition against ß-hemolytic Streptococcus group A at 30 µg/mL. These pyridyl sulfides 4a-d, 5 and 6 represent a new group of antimicrobial agents. Antioxidative activity was analyzed using the DPPH assay. The sulfides 4a-d, 5 and 6 show only a weak antioxidative activity. In contrast the 2-(1-adamantylthio)-3-bromopyridine (4d) shows the highest radical scavenging activity

Antimalarial and antimicrobial activities of 8-aminoquinoline-uracils metal complexes

8-Aminoquinoline (8AQ) derivatives have been reported to have antimalarial, anticancer, and antioxidant activities. This study investigated the potency of 8AQ-5-substituted (iodo and nitro) uracils metal (Mn, Cu, Ni) complexes (1-6) as antimalarial and antimicrobial agents. Interestingly, all of these metal complexes (1-6) showed fair antimalarial activities. Moreover, Cu complexes 2 (8AQ-Cu-5Iu) and 5 (8AQ-Cu-5Nu) exerted antimicrobial activities against Gram-negative bacteria including P. shigelloides and S. dysenteriae. The results reveal application of 8AQ and its metal complexes as potential compounds to be further developed as novel antimalarial and antibacterial agents

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

Bioactive 4-hydroxycinnamide and bioactivities of Polyalthia cerasoides

Constituents from Polyalthia cerasoides, stem bark methanol extract, were previously documented. This study reports the first isolation of bioactive N-(4-hydroxy-β-phenethyl)-4-hydroxycinnamide (1) from ethyl acetate extract of the plant species including stigmasterol and a mixture of triterpenes from hexane and dichloromethane extracts. Trace essential elements were found in the hexane extract in ppm level. The plant extracts were evaluated for their antimicrobial and antioxidative activities. The dichloromethane extract displayed the highest activity against Corynebacterium diphtheriae NCTC 10356 with MIC of 32 μg/mL, as well as, the highest SOD activity with an IC50 of 4.51 μg/mL

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