Chavi Yenjai

Claurailas A−D, Cytotoxic Carbazole Alkaloids from the Roots of Clausena harmandiana

Four new carbazole alkaloids, claurailas A-D (1-4), as well as 12 known carbazoles and three known coumarins were isolated from the roots of Clausena harmandiana. Heptaphylline (6) and 7-methoxyheptaphylline (7) showed strong cytotoxicity against NCI-H187 and KB cell lines with IC(50) values ranging from 1.3 to 2.7 μM. Compound 7 showed no cytotoxicity against Vero cells.

Synthesis, biological evaluation and molecular modeling study of novel tacrine–carbazole hybrids as potential multifunctional agents for the treatment of Alzheimer's disease

New tacrine-carbazole hybrids were developed as potential multifunctional anti-Alzheimer agents for their cholinesterase inhibitory and radical scavenging activities. The developed compounds showed high inhibitory activity on acetylcholinesterase (AChE) with IC50 values ranging from 0.48 to 1.03 μM and exhibited good inhibition selectivity against AChE over butyrylcholinesterase (BuChE). Molecular modeling studies revealed that these tacrine-carbazole hybrids interacted simultaneously with the catalytic active site (CAS) and the peripheral anionic site (PAS) of AChE. The derivatives containing methoxy group showed potent ABTS radical scavenging activity. Considering their neuroprotection, our results indicate that these derivatives can reduce neuronal death induced by oxidative stress and β-amyloid (Aβ). Moreover, S1, the highest potency for both radical scavenging and AChE inhibitory activity, exhibited an ability to improve both short-term and long-term memory deficit in mice induced by scopolamine. Overall, tacrine-carbazole derivatives can be considered as a candidate with potential impact for further pharmacological development in Alzheimers therapy.

Biological activity of chemical constituents from Clausena harmandiana

The activity guided fractionation of the Clausena harmandiana root extracts led to the isolation of a coumarin, a ferulate, and eight carbazoles. This is the first report of the isolation of compounds 2–4 and 6–10 from this species, and this is the first time 10 was isolated from this genus. Compound 4 showed strong cytotoxicity against NCI-H187 cells with an IC50 value of 1.63 μg/mL. Compound 5 demonstrated strong cytotoxicity against MCF-7 and KB cell lines with IC50 values of 2.21 and 1.74 μg/mL, respectively. Compounds 3 and 4 exhibited moderate cytotoxicity against the MCF-7 cell line, and 8 showed moderate cytotoxicity against NCIH187 and KB cell lines. Compounds 3 and 5 showed antiplasmodial activity with IC50 values of 3.27 and 2.94 μg/mL, respectively.

One-step recyclization of sugar acetylenes to form medium ether rings via dicobalthexacarbonyl complexes☆

Four C-1 alkynylated D-glucals were converted into the corresponding dicobalthexacarbonyl complexes. All of them were recyclized upon treatment with acid to form the medium size (7, 8, 9 and 10 membered) ether rings. The crucial mechanism was cis-trans double bond isomerization of allylic cation connected to dicobalthexacarbonyl complexes. Decomplexation was successfully achieved under high pressure hydrogenation by using rhodium catalyst.

Cytotoxicity against KB and NCI-H187 cell lines of modified flavonoids from Kaempferia parviflora.

Flavones 1-4 isolated from Kaempferia parviflora were used for structural modification. Sixteen flavonoid derivatives, including four new derivatives, were synthesized and evaluated for cytotoxicity against KB and NCI-H187 cell lines. Flavanones 2a-4a demonstrated higher cytotoxic activity than the parent compounds. Cytotoxicity against KB cell line of oxime 1c was about 7 times higher than the ellipticine standard. Interestingly, oximes 1c and 2c exhibited highly potent cytotoxicity against NCI-H187 cell line with IC(50) values of 0.014 and 0.23 microM, respectively. Oximes 4c and 5c showed strong cytotoxicity against NCI-H187 cell line with IC(50) values of 4.04 and 2.32 microM, respectively.

Structural modification of 5,7-dimethoxyflavone from Kaempferia parviflora and biological activities

Abstract5,7-Dimethoxyflavone, a major compound from Kaempferia parviflora, was used as a starting material for structural modification. Seven flavonoid derivatives have been synthesized from this flavone. Two new oxime derivatives 4 and 6 exhibited cytotoxicity against HepG2 cell line with IC50 values of 36.38 and 25.34 µg/mL, respectively, and against T47D cell line with IC50 values of 41.66 and 22.94 µg/mL, respectively. Compound 7 showed cytotoxicity against HepG2 and T47D cell lines with IC50 values of 21.36 and 25.00 µg/mL, respectively. Compounds 6 and 7 showed cytotoxicity nearly equal to the tamoxifen standard. In addition, oxime 6 exhibited antifungal activity against Candida albicans with an IC50 value of 48.98 µg/mL.

New lignan esters from Alyxia schlechteri and antifungal activity against Pythium insidiosum.

Three new lignan esters, alyterinates A-C (1-3), as well as 10 known compounds were isolated from the roots of Alyxia schlechteri. Antifungal activity against Pythium insidiosum of all lignan derivatives was evaluated using disk diffusion assay. P. insidiosum is not a true fungus since its cell walls do not contain ergosterol as usual fungi, so the antifungals available now are not effective. From activity testing, it was found that compounds 3, 4 and 5 could inhibit the mycelia growth of P. insidiosum.

Synthesis and cytotoxic activity of the heptaphylline and 7-methoxyheptaphylline series

Nineteen carbazole alkaloids modified from heptaphylline (I) and 7-methoxyheptaphylline (II) isolated from Clausena harmandiana were synthesized. Among these derivatives, Ih and IIi showed cytotoxicity against the NCI-H187 cell line with IC(50) values of 0.02 and 0.66 μM, respectively, which are about 138 and 4 fold stronger than the ellipticine standard. In addition, oxime Ih displayed cytotoxicity against KB cells with an IC(50) value of 0.17 μM which is about 10 times stronger than the ellipticine. This compound demonstrated weak cytotoxicity against Vero cells (IC(50) = 66.01 μM). The results show convincingly that Ih may be a promising lead for the development of cytotoxic agents.

Cytotoxicity against cholangiocarcinoma cell lines of zerumbone derivatives

Cholangiocarcinoma (CCA) is an aggressive malignancy with a very high morbidity and mortality for which an effective treatment is lacking. In this study, seventeen zerumbone derivatives were synthesized and evaluated for in vitro cytotoxicity against cholangiocarcinoma cell lines. 5 showed the most potent antiproliferative activity against KKU-100 cell line with an IC(50) value of 16.44 microM. To investigate the potential molecular target of the most active compound, the docking was performed using different enzymes and receptor proteins including CDK-2, CDK-5, EGFR, and GSK-3. The docking results revealed that 5 exhibited better binding interaction to EGFR than CDK-2, CDK-5 and GSK-3. All results indicate that 5 should be a promising candidate for treatment of cancer.

Bioactive constituents from the stems of Dalbergia parviflora.

From the stems of Dalbergia parviflora, three known flavonoids, six known isoflavonoids, a new isoflavone, dalparvone (2) and a new cinnamyl derivative, dalparvinene (6) were isolated and characterized. Isoflavan 3 exhibited strong cytotoxicity against KB and NCI-H187 cell lines with IC(50) values of 0.53 and 2.04 microg/ml, respectively. Compound 6 demonstrated strong cytotoxicity against NCI-H187 with an IC(50) value of 1.46 microg/ml. Compounds 4 and 6 possessed moderate cytotoxicity against KB cells with IC(50) values of 6.78 and 9.89 microg/ml, respectively. In addition, 2 exhibited moderate antiplasmodial activity with an IC(50) value of 8.19 microg/ml.