Sumit Dey

The caspase-independent algorithm of programmed cell death in Leishmania induced by baicalein: the role of LdEndoG, LdFEN-1 and LdTatD as a DNA 'degradesome'

In the post-genomic perspective, the quest of programmed cell death (PCD) mechanisms in kinetoplastid parasites lies in the identification and characterization of cell death executer proteins. Here, we show that baicalein (BLN), a potent topoisomerase IB inhibitor, generates an oxidative stress in the parasites leading to altered physiological and morphological parameters, which are characteristic of PCD. For the first time we elucidate that, caspase-independent activation of a novel effector molecule, endonuclease G (LdEndoG), mediates BLN-induced cell death. Functional characterization of LdEndoG identifies Flap endonuclease-1 (LdFEN-1) and LdTatD-like nuclease as other effector molecules. BLN treatment translocates LdEndoG from mitochondria to nucleus, where it forms separate complexes with LdFEN-1 and LdTatD to constitute a DNA ‘degradesome’ unique to these parasites. Conditional antisense knockdown of LdEndoG provides protection against PCD. This knowledge paves the path toward a better understanding of the PCD pathway in simpler systems, which could be exploited in anti-leishmanial chemotherapy.

Gold (I) N-heterocyclic carbene complex inhibits mouse melanoma growth by p53 upregulation.

BackgroundCancer treatment using gold (I) complexes is becoming popular. In this study, a gold (I) N-heterocyclic complex designated as complex 3 was synthesized, its cytotoxicity was examined, and its anti-melanoma activity was evaluated in vitro and in vivo.MethodsViability of cancer cells was determined by MTT assay upon treatment with various concentrations of a gold (I) N-heterocyclic carbene complex (complex 3) in a dose and time dependent manner. Mouse melanoma cells B16F10 were selected for further apoptotic studies, including flowcytometric analysis of annexin binding, cell cycle arrest, intracellular ROS generation and loss in the mitochondrial membrane potential. ELISA based assays were done for caspase activities and western blots for determining the expression of various survival and apoptotic proteins. Immunocytology was performed to visualize the translocation of p53 to the nucleus. B16F10 cells were inoculated into mice and post tumor formation, complex 3 was administered. Immunohistology was performed to determine the expressions of p53, p21, NF-κB (p65 and p50), MMP-9 and VEGF. Student’s t test was used for determining statistical significance. The survival rate data were analyzed by Kaplan-Meier plots.ResultsComplex 3 markedly inhibited the growth of HCT 116, HepG2, and A549, and induced apoptosis in B16F10 cells with nuclear condensation, DNA fragmentation, externalization of phosphatidylserine, activation of caspase 3 and caspase 9, PARP cleavage, downregulation of Bcl-2, upregulation of Bax, cytosolic cytochrome c elevation, ROS generation, and mitochondrial membrane potential loss indicating the involvement of an intrinsic mitochondrial death pathway. Further, upregulation of p53, p-p53 (ser 15) and p21 indicated the role of p53 in complex 3 mediated apoptosis. The complex reduced tumor size, and caused upregulation of p53 and p21 along with downregulation of NF-κB (p65 and p50), VEGF and MMP-9. These results suggest that it induced anti-melanoma effect in vitro and in vivo by modulating p53 and other apoptotic factors.ConclusionsThe gold (I) N-heterocyclic carbene complex (C22H26N6AuO2PF6) designated as complex 3 induced ROS and p53 dependent apoptosis in B16F10 cells involving the mitochondrial death pathway along with suppression of melanoma tumor growth by regulating the levels of pro and anti apoptotic factors (p53, p21, NF-κB, VEGF and MMP-9).

Fe-HCl: An Efficient Reagent for Deprotection of Oximes as well as Selective Oxidative Hydrolysis of Nitroalkenes and Nitroalkanes to Ketones

Abstract Fe‐HCl mixture was found to selectively perform oxidative hydrolysis of the nitroalkenes 1a–j and nitroalkanes 2a–j to the ketones 3a–j. Also, the reagent was observed to deprotect the oximes 7a–j to carbonyl compounds 8a–j in excellent yields.

Antibacterial Activity and Anticorrosive Efficiency of Aqueous Methanolic Extract of Artemisia pallens (Asteraceae) and its major Constituent

An aqueous-methanolic [methanol:water (1:1)] extract of the whole plant of Artemisia pallens (Family: Asteraceae) has shown good antibacterial activity against Pseudomonas aeruginosa and Shigella flexneri at the concentration of 100 mg/mL. The activity-guided fractionation has led to isolation of compound 4-hydroxyphenyl-?-D-glucopyranoside (which is known as arbutin), as a major constituent and exhibited the same antibacterial activity at a concentration of 17 mg/mL. Both the crude extract and arbutin also showed 94% anticorrosive efficiency against mild steel in 1M HCl at concentration of 200 mg/L.

Selective reduction of aldehydes to alcohols using alumina with a catalytic amount of base under microwave irradiation

Abstract Aldehydes are selectively reduced to the corresponding alcohols in very good yields with alumina containing a catalytic amount of base under microwave irradiation at 300 W for 8–15 min.