Nitirat Chimnoi

Labdane diterpenes from the rhizomes of Hedychium coronarium

A new labdane diterpenoid, (E)-labda-8(17),12-dien-15,16-olide (1) together with eight known compounds, coronarin D (2), coronarin D methyl ether (3), coronarin D ethyl ether (4), isocoronarin D (5), coronarin B (6), labda-8(17),11,13-trien-15,16-olide (7), (E)-labda-8(17),12-diene-15,16-dial (8) and 16-hydroxylabda-8(17),11,13-trien-15,16-olide (9), are isolated from the rhizomes of Hedychium coronarium. Compounds 2–4, 5 and 9 are isolated as mixtures of C-15, C-14 and C-16 epimers, respectively. Their structures are determined on the basis of their spectroscopic data. The epimeric mixtures of 2 and 3 have not been reported before. Some of them were evaluated for their cytotoxicity.

Cytotoxic and antimicrobial activities of aporphine alkaloids isolated from Stephania venosa (Blume) Spreng.

The cytotoxic activity of five alkaloids, namely 4,5-dioxo-dehydrocrebanine (1), dehydrocrebanine (2), crebanine (3), oxostephanine (4), and thailandine (5) isolated from the tuber and leaves of Stephania venosa (Blume) Spreng was investigated. Thailandine showed the strongest activity against lung carcinoma cells (A549) (IC50 of 0.30 µg/mL) with very low cytotoxicity against normal embryonic lung cells (MRC-5). Thailandine also demonstrated strong activity against Plasmodium falciparum, K1 strain (IC50 of 20 ng/mL), and Mycobacterium tuberculosis H(37)Ra (MIC of 6.25 µg/mL) as well as gram-positive bacteria such as Streptococcus pneumoniae and Staphylococcus aureus. Oxostephanine exhibited strong activity against breast cancer (BC) and acute lymphoblastic leukemia cells (MOLT-3) with an IC50 of 0.24 and 0.71 µg/mL, respectively, and exhibited very low cytotoxicity against MRC-5 cells. Dehydrocrebanine demonstrated strong activity against promyelocytic leukemia cells (HL-60) with an IC50 of 2.14 µg/mL whereas crebanine showed weak activity against cancer cell lines. However, both of them showed cytotoxicity against MRC-5 cells.

Chemical modifications at the 22-hydroxyl group of ecdysteroids: alternative structural requirements for high moulting activity.

A number of 22-O-alkyl ether and acyl ester derivatives have been prepared and their moulting activity determined, using the Musca assay. It was found that a free 22-hydroxyl group is not an essential structural requirement for an ecdysteroid to exhibit high moulting activity. The activity of a 22-O-substituted ecdysteroid may even be higher than that of the parent compound, providing that the substituent constitutes a functional group that can enhance biological activity. The moulting activity is not sensitive to steric factors at the 22-position. Ecdysteroid without a 22-hydroxyl group may exhibit high moulting activity if a functional group that can enhance activity is present at an appropriate position.

Synthesis and anti-acetylcholinesterase activity of scopoletin derivatives.

A series of scopoletin derivatives incorporated with the pyridinium moiety was synthesized and evaluated for their acetylcholinesterase (AChE) inhibitory activity by the colorimetric Ellmans method. A 2-fluorobenzylpyridinium derivative was the most potent among the tested compounds, with an IC50 value of 0.215±0.015μM, which was greatly improved from that of scopoletin. Docking studies revealed that the scopoletin portion of the mentioned compound was bound to the peripheral anionic site of the AChE, whereas the N-benzylpyridinium residue to the catalytic anionic site.

Antimicrobial Activity of Coronarin D and Its Synergistic Potential with Antibiotics

Coronarin D is a labdane-type diterpene from the rhizomes of Hedychium coronarium. In the view of our ongoing effort to explore its novel biological activity, antimicrobial activity study of coronarin D was performed. The results showed that coronarin D was active against tested Gram-positive bacteria, inactive for tested Gram-negative bacteria, and weakly active against tested fungi. The antibacterial effect of the combination of coronarin D with nine classical antibiotics against four Gram-positive bacteria was also evaluated. The fractional inhibitory concentration indices (FICI) of coronarin D-antibiotics combinations, calculated from the checkerboard assay, were used as synergism indicator. Out of 36 combinations, 47% showed total synergism, 33% had partial synergistic interaction, 17% showed no effect, and 3% showed antagonism. By combination with coronarin D at concentration of 0.25 minimal inhibitory concentration (MIC), the activities of antibiotics were boosted to 4- to 128-fold. These finding suggested an attractive approach to combat the infectious diseases by using coronarin D-antibiotic drug combination.

C-25 epimeric 26-haloponasterone A: Synthesis, absolute configuration and moulting activity

A convenient synthesis of inokosterone has been accomplished. Inokosterone exists as two C-25 epimers, which could be separated from each other through their diacetonide derivatives. The absolute configuration of these compounds was determined. Two C-25 epimers of 26-chloroponasterone A were synthesized from the respective C-25 epimeric inokosterone. Two epimeric 26-bromo and 26-iodoponasterone A compounds were also synthesized. Moulting activity of these compounds was evaluated using the Musca bioassay, and it was found that the (25S)-26-halo analogues were more active than the corresponding (25R)-26-halo analogues. Among the 25S series, an increase in activity with an increase in size of the halogen atom was observed, indicating that the steric factor was more important than the electronic factor in binding of these ecdysteroid analogues to the receptor. On the other hand, a decrease in activity with an increase in size of the halogen atom was noted in the 25R series, suggesting that the steric factor was less important than the electronic factor. The results indicated that the configuration at C-25 and the substituent at C-26 have significant influences on the interaction of ecdysteroids with their receptor.

Antifungal activity of coronarin D against Candida albicans.

OBJECTIVE The objective of this study was to investigate the antifungal activity of coronarin D on Candida albicans and its activity was compared with clotrimazole and nystatin. METHODS Coronarin D was extracted by liquid chromatography and used in antifungal testing. The inhibitory effect of coronarin D on C. albicans was determined by cultures and an applied broth dilution test. The rate of fungicidal activity was evaluated by time-kill curves. Morphologic alterations of fungal cells were investigated using scanning electron microscopy. RESULTS Coronarin D was effective against C. albicans; the minimum inhibitory concentration (MIC) and the minimum fungicidal concentration (MFC) were 2 and 4 mg/mL, respectively. The C. albicans killing activity of coronarin D was higher than clotrimazole and nystatin at 2 × MFC and 4 × MFC, respectively. Morphologic alterations of fungal cells consistent with cell membrane damage were observed in the coronarin D-treated cells. CONCLUSIONS Coronarin D showed promising antifungal activity against C. albicans in vitro.

Dipyridodiazepinone derivatives; synthesis and anti HIV-1 activity

Summary Ten dipyridodiazepinone derivatives were synthesized and evaluated for their anti HIV-1 reverse transcriptase activity against wild-type and mutant type enzymes, K103N and Y181C. Two of them were found to be promising inhibitors for HIV-1 RT.

Roscotanes and roscoranes: Oxygenated abietane and pimarane diterpenoids from Kaempferia roscoeana

Eight previously undescribed ditepenoids, including four oxygenated abietanes (roscotanes A-D) and four oxygenated pimaranes (roscoranes A-D), along with twelve known diterpenoids were isolated from the whole plants of Kaempferia roscoeana. Their structures were elucidated by extensive spectroscopic analysis, and the structure of roscotane A was further confirmed by single crystal X-ray diffraction analysis. Most isolated compounds were evaluated for their antimicrobial and antimalarial activities.

Novel 2-Chloro-8-arylthiomethyldipyridodiazepinone Derivatives with Activity against HIV-1 Reverse Transcriptase

Based on the molecular modeling analysis against Y181C HIV-1 RT, dipyridodiazepinone derivatives containing an unsubstituted lactam nitrogen and 2-chloro-8-arylthiomethyl were synthesized via an efficient route. Some of them were evaluated for their antiviral activity against HIV-1 RT subtype E and were found to exhibit virustatic activity comparable to some clinically used therapeutic agents.