Ruchi Tyagi

Inhibitors of Cyclin Dependent Kinases: Useful Targets for Cancer Treatment

Cancer drug discovery is one of the most rapidly changing areas of pharmaceutical research. Uncontrolled proliferation is a hallmark of cancer cells. Over the past two decades, it has become increasingly clear that in many human cancers, hyperactivity of Cyclin Dependent Kinases (CDKs) is one of the mechanisms underlying the physiological hyper-proliferation. CDKs are serine/threonine protein kinases, which play an important role in cell-cycle regulation. Their sequential activation ensures, the correct timing and ordering of events required for cell cycle progression. Therefore, inhibition of CDKs, through the insertion of small molecules into its ATP binding pocket has emerged as a potential therapy method for cancers. Consequently, a number of small molecules with CDK inhibitory properties have been developed. Many of these have been evaluated as potent inhibitors and some are currently in clinical-trials for various types of cancer. This review reports various CDK inhibitors, natural as well as small molecules, along with their reported activities for various CDKs. It will highlight the potential for the development of novel anti-cancer molecules.

Noteworthy Mechanistic Precedence in the Exclusive Formation of One Regioisomer in the Beckmann Rearrangement of Ketoximes of 4-Piperidones Annulated to Pyrazolo-indole Nucleus by Organocatalyst Derived from TCT and DMF

Abstract Application of a very mild protocol to the Beckmann rearrangement of ketoximes of pyrazolo annulated oxocarbazole 5a and oxoazacarbazole 5b with the organocatalyst derived from 2,4,6-trichloro[1,3,5]triazine (TCT) and dimethylformamide (DMF) has been explored to provide a regioselective formation of the corresponding azepine 6a and 1,4-diazepine 6b respectively in good yield and purity. The mechanistic precedence for the exclusive formation of only one regioisomer has been discussed. GRAPHICAL ABSTRACT

An Expedient Protocol to the Synthesis of Benzo(b)furans by Palladium Induced Heterocyclization of Corresponding 2-Allylphenols Containing Electron Rich and Electron Capturing Substituents in the Arene Ring

A facile and rapid accessibility to the libraries containing several mono, and disubstituted benzo(b)furan derivatives substituted with a variety of electron rich and electron capturing groups on 2, 4, 5, 6, and 7 positions of its nucleus has been explored using the PdCl2(CH3CN)2 catalyzed heterocyclization of the corresponding 2-allylphenols to afford 2(a–m) in good yield and high purity.

Synthesis of novel precursors of Pfitzinger reaction: A facile one-pot strategy to the synthesis of quinoline carboxylic acid derivatives of pyrazolo-carbazoles and azacarbazoles

AbstractInteraction of 5-indazolyldiazonium chloride 2 with 2-hydroxymethylidene cyclohexanone 5 and N-benzyl-3-hydroxymethylidene-4-piperidone 6 under the conditions of Japp–Klingemann reaction, followed by Fischer-indolization of the resulting hydrazones, formed the 5,7,8,9-tetrahydropyrazolo[4,3-b]carbazol-6(1H)-one 9 and 9-benzyl-5,7,8,9-tetrahydropyrido[2′,3′:4,5]pyrrolo[2,3-f]indazol-6(1H)-one 10, respectively. Pfitzinger reaction of 9 and 10 with isatin in alkali afforded the corresponding quinoline carboxylic acid derivatives 12 and 13, respectively. Graphical AbstractQuinoline carboxylic acid derivatives of pyrazolo-carbazoles and azacarbazoles have been synthesized from 5-indazolyldiazonium chloride 2 and 2-hydroxymethylidene cyclohexanone 5 or N-benzyl-3-hydroxymethylidene- 4-piperidone 6 by applying the strategy of Japp-Klingemann reaction and Fischer-indolization followed by Pfizinger reaction.

Morpho-Physiological Attributes of Cultivated Wheat Germplasm for high yield potential under Rain fed condition

Wheat is the most important cereal crop and staple diet for more than one third of the world population and contributes more calories and protein to the world diet than any other cereal crop. In view of global climate change drought stress is becoming major constraints for the productivity of wheat and hence the breeding for drought tolerance is gaining more importance. More accurate and precise phenotyping of genetic resources is the demand of the new generation quantitative geneticists and plant breeders as this is the most critical research area which will lead to identification of trait specific donor germplasm. In the present study, Wheat germplasm accessions (1483 acc.) were evaluated at Issapur farm in Augmented Block Design with four checks based on morpho-physiological parameters. Irrigation was provided at Crown root initiation stage (CRI) and afterwards moisture deficit was maintained throughout the crop duration. There was wide variability in wheat germplasm for the phonological, agronomical and physiological traits. This experiment identified correlated traits responsible for high grain yield under rainfed conditionsuch as biological yield, harvest index, days to maturity, spike length, spikelets per spike, grains per spike, cholorophyll content, grain weight and 1000 grain weight. Based on stepwise multiple regression analysis, major role of prediction on yield was found through biological yield, including harvest index, grain weight spikelets per spike and chlorophyll content. Based on predictor variables, accessions were selected and will be further validated under controlled condition and will be used for introgression purpose in the background of elite varieties to enhance yield and its stability under moisture stress environments.

Development of Core Set of Wheat ( Triticum spp. ) Germplasm Conserved in the National Genebank in India

Plant genetic resources, the source of genetic diversity provides a broad genetic foundation for plant breeding and genetic research, however, large germplasm resources are difficult to preserve, evaluate and use. Construction of core and mini core collections is an efficient method for managing genetic resources and undertaking intensive surveys of natural variation, including the phenotyping of complex traits and genotyping of DNA polymorphisms allowing more efficient utilization of genetic resources. A mega characterization and evaluation programme of the entire cultivated gene pool of wheat conserved in the National Genebank, India was undertaken. Wheat accessions with limited seed quantity, were multiplied in the off-season nursery at IARI Regional Station, Wellington during rainy season 2011 and the entire set of 22,469 wheat accessions were characterized and evaluated at CCS HAU, Hisar, Haryana during winter season 2011–12 for 34 characters including 22 highly heritable qualitative, and 12 quantitative parameters. The core sets were developed using PowerCore Software with stepwise approach and grouping method and validated using Shannon-Diversity Index and summary statistics. Based on Shannon-Diversity index, PowerCore with stepwise approach was found better than PowerCore with grouping. The core set included 2,208 accessions comprising 1,770 T. aestivum, 386 T. durum, and 52 T. dicoccum accessions as a representative of the total diversity recorded in the wheat germplasm. The core set developed will be further validated at different agro-climatic conditions and will be utilized for development of mini core set to enhance the utilization by wheat researchers and development of climate resilient improved varieties.