Zerumbone, a Cyclic Sesquiterpene from Zingiber zerumbet Induces Apoptosis, Cell Cycle Arrest, and Antimigratory Effects in SW480 Colorectal Cancer Cells.

Zerumbone isolated from the rhizomes of Zingiber zerumbet was investigated for the mechanisms by which it exhibits antiproliferative activity in colorectal cancer cells (SW480). The results indicated that the zerumbone suppressed cell growth and enhanced cell apoptosis. Exposure to zerumbone induced generation of reactive oxygen species, reduced the cellular antioxidant status, decreased mitochondrial membrane potential, and activated caspase 3, caspase 8, and caspase 9 (p < 0.001). It was also found that there was a decrease in the expression of Bcl 2 and elevation of Bax (p < 0.001) on exposure to zerumbone. Furthermore, treatment with 50, 75, and 100 µM zerumbone resulted in cell cycle arrest at the G2/M phase with a value of 17.2 ± 0.1, 19.63 ± 0.25, and 26.66 ± 0.25, respectively, and also distorted the microfilament network and effectively inhibited cellular migration.

Effects of a new synthetic zerumbone pendant derivative (ZPD) on apoptosis induction and anti-migratory effects in human cervical cancer cells.

A newly synthesised zerumbone pendant derivative (ZPD) was studied in human cervical cancer cells (HeLa) for its anticancer properties. ZPD significantly inhibited the growth of human cervical cancer cells with a GI50 value of 6.35 ± 1.30 µM, which also induced morphological changes and apoptosis in a dose-dependent manner. Our data indicated that ZPD actively encouraged programmed cell death in HeLa cells which were confirmed by DNA fragmentation, phosphatidylserine translocation, increased activity of caspase 3, upregulation of the expression of the pro-apoptotic protein Bax, cleaved PARP, cleaved caspase 3 and downregulation of anti-apoptotic protein Bcl-2. ZPD also inhibited cell migration of HeLa cells, decreasing the production of MMP-2,-9 and downregulation of expression of MMPs and pro-angiogenic factor VEGF. Also it is nontoxic to normal rat cardiac myoblasts. Overall, ZPD is a promising candidate for inducing cytotoxicity, apoptosis and anti-migratory effects in cervical cancer cells.

Studies on α-glucosidase, aldose reductase and glycation inhibitory properties of sesquiterpenes and flavonoids of Zingiber zerumbet Smith.

Eight known phytochemicals, four sesquiterpenes and four flavonoids of Zingiber zerumbet were screened against α-glucosidase enzyme, aldose reductase enzyme and antiglycation property under in vitro conditions. The results established kaempferol-3-O-methylether as a potent inhibitor of α-glucosidase enzyme with an IC50 value of 7.88 µM. In aldose reductase enzyme inhibition assay, all the compounds except zerumbone epoxide showed good to excellent inhibition properties. Among these, the flavonoid compounds were found to be potent aldose reductase inhibitors compared with the four sesquiterpenes. In addition, compounds such as α-humulene, kaempferol, kaempferol-3-O-methylether and 3″,4″-O-diacetylafzelin displayed potent antiglycation properties. From overall results, we found that kaempferol and kaempferol-3-O-methylether are potent inhibitors of α-glucosidase enzyme, aldose reductase enzyme and glycation reaction, the three main targets of drugs for the treatment of diabetes and its complications.

Trapping the Lewis acid generated transient species from pentafulvene derived diazanorbornenes with ortho-functionalized aryl iodides and aliphatic alcohols.

Herein we describe our efforts on the Lewis acid catalyzed stereoselective ring-opening of pentafulvene derived diazabicyclic olefins using various ortho-functionalized aryl iodides such as 2-iodoanilines, 2-iodophenols and 2-iodobenzene thiols to access trans-1,2 disubstituted alkylidenecyclopentenes. The scope of the reaction was also explored with a range of easily available aromatic and aliphatic alcohols. Furthermore, the palladium catalyzed intramolecular Heck cyclization of trans-1,2 disubstituted alkylidenecyclopentenes would provide an easy approach for the synthesis of highly functionalized spiropentacyclic frameworks consisting of a cyclopentene fused to an indoline/benzothiophene and pyrazolidine.

Palladium/Lewis acid mediated domino reaction of pentafulvene derived diazabicyclic olefins: efficient access to spiropentacyclic motif with an indoline and pyrazolidine fused to cyclopentene.

A palladium/Lewis acid mediated stepwise and one-pot transformation of pentafulvene derived diazabicyclic olefins is described. The reaction offers a facile strategy for the synthesis of novel spiropentacyclic motifs with indoline and pyrazolidine fused to the cyclopentene core.