@article { ISI:000354004400014, title = {Breaking and making of olefins simultaneously using ozonolysis: application to the synthesis of useful building blocks and macrocyclic core of solomonamides}, journal = {Organic Letters}, volume = {17}, number = {9}, year = {2015}, month = {MAY}, pages = {2090-2093}, publisher = {AMER CHEMICAL SOC}, address = {1155 16TH ST, NW, WASHINGTON, DC 20036 USA}, abstract = {

A simple and practical one-pot) two-directional approach to access olefinic esters through simultaneous breaking and making of olefins using ozonolysis of alkenyl aryl selenides is disclosed The scope of the method with a variety of example{\textquoteright}s is demonstrated, and the end products obtained here are useful building blocks. As a direct application of the present method,the macrocyclic cote of potent anti-inflammatory natural cyclic peptides, solomonamides, is synthesized.

}, issn = {1523-7060}, doi = {10.1021/acs.orglett.5b00637}, author = {Kashinath, K. and Dhara, Santu and Reddy, D. Srinivasa} } @article { ISI:000366429100003, title = {Breaking and making of rings: a method for the preparation of 4-quinolone-3-carboxylic acid amides and the expensive drug ivacaftor}, journal = {European Journal of Organic Chemistry}, number = {34}, year = {2015}, month = {DEC}, pages = {7433-7437}, publisher = {WILEY-V C H VERLAG GMBH}, address = {POSTFACH 101161, 69451 WEINHEIM, GERMANY}, abstract = {

A simple and convenient method to access 4-quinolone-3-carboxylic acid amides from indole-3-acetic acid amides through one-pot oxidative cleavage of the indole ring followed by condensation (Witkop-Winterfeldt type oxidation) was explored. The scope of the method was confirmed with more than 20 examples and was successfully applied to the synthesis of the drug Ivacaftor, the most expensive drug on the market.

}, keywords = {Amides, Drug design, Fused-ring systems, Oxidation, Ozonolysis}, issn = {1434-193X}, doi = {10.1002/ejoc.201501048}, author = {Vasudevan, N. and Jachak, Gorakhnath R. and Reddy, D. Srinivasa} } @article {46671, title = {Biological process of lysine-tRNA charging is therapeutically targetable in liver cancer}, journal = {Liver International}, volume = {41}, year = {2021}, month = {JAN }, pages = {206-219}, type = {Article }, abstract = {

Background \& Aims Mature transfer RNAs (tRNA) charged with amino acids decode mRNA to synthesize proteins. Dysregulation of translational machineries has a fundamental impact on cancer biology. This study aims to map the tRNAome landscape in liver cancer patients and to explore potential therapeutic targets at the interface of charging amino acid with tRNA. Methods Resected tumour and paired tumour-free (TFL) tissues from hepatocellular carcinoma (HCC) patients (n = 69), and healthy liver tissues from organ transplant donors (n = 21), HCC cell lines, and cholangiocarcinoma (CC) patient-derived tumour organoids were used. Results The expression levels of different mature tRNAs were highly correlated and closely clustered within individual tissues, suggesting that different members of the tRNAome function cooperatively in protein translation. Interestingly, high expression of tRNA-Lys-CUU in HCC tumours was associated with more tumour recurrence (HR 1.1;P = .022) and worse patient survival (HR 1.1;P = .0037). The expression of Lysyl-tRNA Synthetase (KARS), the enzyme catalysing the charge of lysine to tRNA-Lys-CUU, was significantly upregulated in HCC tumour tissues compared to tumour-free liver tissues. In HCC cell lines, lysine deprivation, KARS knockdown or treatment with the KARS inhibitor cladosporin effectively inhibited overall cell growth, single cell-based colony formation and cell migration. This was mechanistically mediated by cell cycling arrest and induction of apoptosis. Finally, these inhibitory effects were confirmed in 3D cultured patient-derived CC organoids. Conclusions The biological process of charging tRNA-Lys-CUU with lysine sustains liver cancer cell growth and migration, and is clinically relevant in HCC patients. This process can be therapeutically targeted and represents an unexplored territory for developing novel treatment strategies against liver cancer.

}, keywords = {Cladosporin, liver cancer, lysine, Lysyl-tRNA Synthetase, tRNA-Lys-CUU, tRNAome}, issn = {1478-3223}, doi = {10.1111/liv.14692}, author = {Zhang, Ruyi and Noordam, Lisanne and Ou, Xumin and Ma, Buyun and Li, Yunlong and Das, Pronay and Shi, Shaojun and Liu, Jiaye and Wang, Ling and Li, Pengfei and Verstegen, Monique M. A. and Reddy, D. Srinivasa and van Der Laan, Luc J. W. and Peppelenbosch, Maikel P. and Kwekkeboom, Jaap and Smits, Ron and Pan, Qiuwei} }