Semi-synthesis and bio-evaluation of polybrominated diphenyl ethers from the sponge Dysidea herbacea

The sponge Dysidea herbacea was collected from the Mandapam Coast, Tamilnadu, India. Isolated gram quantities of hydroxylated polybrominated diphenyl ether (HO-PBDE) and semi-synthesized a series of new PBDEs derivatives and tested them for antibacterial and cytotoxic activities.     

Anti-cancer evaluation of carboxamides of furano-sesquiterpene carboxylic acids from the soft coral Sinularia kavarattiensis

The chemical investigation of soft coral Sinularia kavarattiensis is described. It yielded furano-sesquiterpene carboxylic acids 1 and 2 and their methyl esters 3 and 4. Semi-synthesis of furano-sesquiterpene carboxylic acid 1 gave amide derivatives 5–12. Structures of all the compounds were established by IR, NMR and mass spectral analysis. Interestingly all compounds are selectively potent on leukemia cell line. All these compounds were screened for cytotoxic activity against five human cancer cell lines (leukemia, prostate, lung, breast and cervix). Among these compounds 9 and 10 showed promising activity against leukemia and prostate cancer cell lines.     

Cell cycle–related metabolism and mitochondrial dynamics in a replication-competent pancreatic beta-cell line

Cell replication is a fundamental attribute of growth and repair in multicellular organisms. Pancreatic beta-cells in adults rarely enter cell cycle, hindering the capacity for regeneration in diabetes. Efforts to drive beta-cells into cell cycle have so far largely focused on regulatory molecules such as cyclins and cyclin-dependent kinases (CDKs). Investigations in cancer biology have uncovered that adaptive changes in metabolism, the mitochondrial network, and cellular Ca²⁺ are critical for permitting cells to progress through the cell cycle. Here, we investigated these parameters in the replication-competent beta-cell line INS 832/13. Cell cycle synchronization of this line permitted evaluation of cell metabolism, mitochondrial network, and cellular Ca²⁺ compartmentalization at key cell cycle stages. The mitochondrial network is interconnected and filamentous at G1/S but fragments during the S and G2/M phases, presumably to permit sorting to daughter cells. Pyruvate anaplerosis peaks at G1/S, consistent with generation of biomass for daughter cells, whereas mitochondrial Ca²⁺ and respiration increase during S and G2/M, consistent with increased energy requirements for DNA and lipid synthesis. This synchronization approach may be of value to investigators performing live cell imaging of Ca²⁺ or mitochondrial dynamics commonly undertaken in INS cell lines because without synchrony widely disparate data from cell to cell would be expected depending on position within cell cycle. Our findings also offer insight into why replicating beta-cells are relatively nonfunctional secreting insulin in response to glucose. They also provide guidance on metabolic requirements of beta-cells for the transition through the cell cycle that may complement the efforts currently restricted to manipulating cell cycle to drive beta-cells through cell cycle.     

Demonstration of a sucrose-derived contrast agent for magnetic resonance imaging of the GI tract

A scaffold bearing eight terminal alkyne groups was synthesized from sucrose, and copies of an azide-terminated Gd–DOTA complex were attached via copper(I)-catalyzed azide-alkyne cycloaddition. The resulting contrast agent (CA) was administered by gavage to C3H mice. Passage of the CA through the gastrointestinal (GI) tract was followed by T₁-weighted magnetic resonance imaging (MRI) over a period of 47 h, by which time the CA had exited the GI tract. No evidence for leakage of the CA from the GI tract was observed. Thus, a new, orally administered CA for MRI of the GI tract has been developed and successfully demonstrated.