Supanna Techasakul

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.

Dalcochinin-8′-O-β-d-glucoside and its β-glucosidase enzyme from Dalbergia cochinchinensis

Abstract Anisoflavonoid glucoside was isolated from the seeds of Thai Rosewood (Dalbergiacochinchinensis Pierre), and the aglycone was shown to be 12-dihydroamorphigenin, which we named dalcochinin. Dalcochinin-8′-O-β- d -glucoside is well hydrolyzed by Thai Rosewood β-glucosidase (Km 1.68 mM), but not by other β-glucosidases, such as cassava stem linamarase, almond β-glucosidase, or mustard seed myrosinase.

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.

Development of a gallic acid-loaded chitosan and polyvinyl alcohol hydrogel composite: Release characteristics and antioxidant activity

The physico-chemical properties of a chitosan and polyvinyl alcohol (CS/PVA)-based hydrogel composite were investigated. Tetraethyl orthosilicate (TEOS) was employed as a crosslinking agent. The results indicated that the chitosan-based composite presented a thermal resistance up to 200°C. The structural properties, which were evaluated using FTIR and DSC, showed good miscibility between chitosan and polyvinyl alcohol. SEM presented a compact and homogeneous structure. The release profile of the chitosan-based hydrogel composite was investigated using gallic acid (GA). It showed high antioxidant activities, which were monitored using DPPH radical scavenging. Diffusion of water into the chitosan-based hydrogel was assumed to be pseudo-Fickian in PBS solution. The CS/PVA-based hydrogel composite exhibited good properties as a drug delivery system.

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.

NMR characterization of HIV-1 reverse transcriptase binding to various non-nucleoside reverse transcriptase inhibitors with different activities

Human immunodeficiency virus type 1 reverse transcriptase (HIV-1 RT) is an important target for antiviral therapy against acquired immunodeficiency syndrome. However, the efficiency of available drugs is impaired most typically by drug-resistance mutations in this enzyme. In this study, we applied a nuclear magnetic resonance (NMR) spectroscopic technique to the characterization of the binding of HIV-1 RT to various non-nucleoside reverse transcriptase inhibitors (NNRTIs) with different activities, i.e., nevirapine, delavirdine, efavirenz, dapivirine, etravirine, and rilpivirine. 1H-13C heteronuclear single-quantum coherence (HSQC) spectral data of HIV-1 RT, in which the methionine methyl groups of the p66 subunit were selectively labeled with 13C, were collected in the presence and absence of these NNRTIs. We found that the methyl 13C chemical shifts of the M230 resonance of HIV-1 RT bound to these drugs exhibited a high correlation with their anti-HIV-1 RT activities. This methionine residue is located in proximity to the NNRTI-binding pocket but not directly involved in drug interactions and serves as a conformational probe, indicating that the open conformation of HIV-1 RT was more populated with NNRTIs with higher inhibitory activities. Thus, the NMR approach offers a useful tool to screen for novel NNRTIs in developing anti-HIV drugs.

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.