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Felnagle E.A.,University of California at Los Angeles | Chaubey A.,University of California at Los Angeles | Chaubey A.,Indian Institute of Integrative Medicine | Noey E.L.,University of California at Los Angeles | And 2 more authors.
Nature Chemical Biology | Year: 2012

Recursive pathways are broadly defined as those that catalyze a series of reactions such that the key, bond-forming functional group of the substrate is always regenerated in each cycle, allowing for a new cycle of reactions to begin. Recursive carbon-chain elongation pathways in nature produce fatty acids, polyketides, isoprenoids and Î ±-keto acids (αKAs), which all use modular or iterative approaches for chain elongation. Recently, an artificial pathway for αKA elongation has been built that uses an engineered isopropylmalate synthase to recursively condense acetyl-CoA with αKAs. This synthetic approach expands the possibilities for recursive pathways beyond the modular or iterative synthesis of natural products and serves as a case study for understanding the challenges of building recursive pathways from nonrecursive enzymes. There exists the potential to design synthetic recursive pathways far beyond what nature has evolved. © 2012 Nature America, Inc. All rights reserved.


Kumar M.,Guru Nanak Dev University | Kumar N.,Guru Nanak Dev University | Bhalla V.,Guru Nanak Dev University | Sharma P.R.,Indian Institute of Integrative Medicine | Kaur T.,Indian Institute of Integrative Medicine
Organic Letters | Year: 2012

A highly selective fluorescent chemodosimeter based on rhodamine is synthesized which undergoes Cu 2+ driven hydrolysis in aqueous media to produce fluorescence turn-on changes with a detection limit up to the nanomolar range. © 2011 American Chemical Society.


Bharate S.S.,P.A. College | Bharate S.B.,Indian Institute of Integrative Medicine
ACS Chemical Neuroscience | Year: 2012

(Figure Presented) ThermoTRPs, a subset of the Transient Receptor Potential (TRP) family of cation channels, have been implicated in sensing temperature. TRPM8 and TRPA1 are both activated by cooling. TRPM8 is activated by innocuous cooling (<30 °C) and contributes to sensing unpleasant cold stimuli or mediating the effects of cold analgesia and is a receptor for menthol and icilin (mint-derived and synthetic cooling compounds, respectively). TRPA1 (Ankyrin family) is activated by noxious cold (<17 °C), icilin, and a variety of pungent compounds. Extensive amount of medicinal chemistry efforts have been published mainly in the form of patent literature on various classes of cooling compounds by various pharmaceutical companies; however, no prior comprehensive review has been published. When expressed in heterologous expression systems, such as Xenopus oocytes or mammalian cell lines, TRPM8 mediated currents are activated by a number of cooling compounds in addition to menthol and icilin. These include synthetic p-menthane carboxamides along with other class of compounds such as aliphatic/alicyclic alcohols/esters/amides, sulphones/sulphoxides/sulphonamides, heterocyclics, keto-enamines/lactams, and phosphine oxides. In the present review, the medicinal chemistry of various cooling compounds as activators of thermoTRPM8 channel will be discussed according to their chemical classes. The potential of these compounds to emerge as therapeutic agents is also discussed. © 2012 American Chemical Society.


Rouf A.,Indian Institute of Integrative Medicine | Taneja S.C.,Indian Institute of Integrative Medicine
Chirality | Year: 2014

Chiral-center enantiomers have been shown to differ significantly in biological activity, pharmacodynamics, pharmacokinetics and toxicity. New developments in the stereoselective organic synthesis have enriched the vast literature of synthetic methodologies applicable to access natural products as well as bioactive molecules. These compounds also include new drugs, drug candidates and reagents used to explore biological processes. The article reviews the synthesis of optically pure drugs, biologically active intermediates and amino alcohols by using different methods. © 2013 Wiley Periodicals, Inc.


Kaul M.K.,Indian Institute of Integrative Medicine
Indian Journal of Traditional Knowledge | Year: 2010

Emerging trends of underutilization of high altitude medicinal plants by Indian phytopharmaceutical industry suggest that therapeutic potential of these species has been exploited to a very less extent despite availability of rich traditional knowledge and also greater possibilities of offering novel bioactive compounds. According to a recent estimate only 20% high altitude medicinal plants available in Indian subcontinent (predominantly herbs) are used in drug trade. In India, we often wake to our own therapeutic wisdom only after recognition comes from the west. High altitude herbal medicines offer therapeutics for many disorders like memory loss, osteoporosis, immune and age-related problems, etc. particularly the ones for which no modern medicines are available. Of late, these plants are also reported to offer satisfactory therapies for deadly diseases like AIDS and cancer. As high altitude plants are growing under stressful situations and exposed to high UV radiations, they are reported to have immense potential in biological radioprotection. An attempt has been made to highlight the promise that these stress-tolerant plants hold in alleviating human and veterinary ailments with less side effects. Studies on the characteristics of ethnopharmacological resources in high altitude Northwest Himalayan region revealing use of 154 botanicals in home remedy patterns of 55 common ailments as well as integration of food and medicine in several traditional herbal therapies are discussed and included in the text.


Bharate S.B.,Indian Institute of Integrative Medicine | Sawant S.D.,Indian Institute of Integrative Medicine | Singh P.P.,Indian Institute of Integrative Medicine | Vishwakarma R.A.,Indian Institute of Integrative Medicine
Chemical Reviews | Year: 2013

The ocean occupies three-fourths of the Earth's surface and hosts approximately 80% of all living species. In fact, some areas of the sea such as coral reefs possess a biodiversity density greater than that of tropical rainforests. A recent census of marine life by 2700 scientists from more than 80 countries assessed the diversity, distribution, and abundance of marine life and reported over 6000 potentially novel species. Molecules with potential biomedical applications include alkaloids, terpenoids, steroids, polypeptides, polyethers, macrolides, and polysaccharides. Marine organisms produce secondary metabolites that are structurally distinct from those produced by terrestrial organisms, due to the unique biosynthetic milieu, and unusual functional groups such as isocyanate, isonitrile, dichloroimine, and halogenated functionalities that are predominantly found in marine metabolites.


Deshidi R.,Indian Institute of Integrative Medicine | Kumar M.,Indian Institute of Integrative Medicine | Devari S.,Indian Institute of Integrative Medicine | Shah B.A.,Indian Institute of Integrative Medicine
Chemical Communications | Year: 2014

A novel catalytic system TMSOTf/I2/DMSO for the oxidative coupling of terminal alkynes with virtually any primary/secondary amine leading to α-ketoamides has been developed. The reaction possibly proceeds via iminium ion formation, wherein DMSO acts as a solvent as well as an oxidizing agent. This journal is © the Partner Organisations 2014.


Kumar A.,Indian Institute of Integrative Medicine | Shah B.A.,Indian Institute of Integrative Medicine
Organic Letters | Year: 2015

A metal-free oxidative coupling of styrenes and benzyl alcohols with arenes has been developed for the synthesis of biaryls. The reaction features a conspicuous benzylic C-C bond cleavage of styrenes and benzyl alcohols. The reaction with both substrates proceeds through a common aldehydic intermediate formed through oxidative C-C bond cleavage of alkene and oxidation of benzyl alcohols. The reaction proceeds efficiently over a broad range of substrates with excellent functional group tolerance. © 2015 American Chemical Society.


Johri R.K.,Indian Institute of Integrative Medicine
Pharmacognosy Reviews | Year: 2011

Cuminum cyminum and Carum carvi are the sources of cumin and caraway seeds respectively, which have been used since antiquity for the treatment of various indications in traditional healing systems in wide geographical areas. Cumin and caraway seeds are rich sources of essential oils and have been actively researched for their chemical composition and biological activities. In recent times (especially during the last 3 years) considerable progress has been made regarding validation of their acclaimed medicinal attributes by extensive experimental studies. In this attempt many novel bioactivities have been revealed. This review highlights the significance of cumin and caraway as potential source of diverse natural products and their medicinal applications.


Najar I.A.,Indian Institute of Integrative Medicine | Johri R.K.,Indian Institute of Integrative Medicine
Journal of Biosciences | Year: 2014

Etoposide, a semi-synthetic derivative of podophyllotoxin, is one of the most active and useful antineoplastic agent used routinely in firstline combination chemotherapy of testicular cancer, small-cell lung cancer and non-Hodgkin's lymphoma. Etoposide displays narrow therapeutic index, erratic pharmacokinetics and dose individualization that needs to be achieved for overcoming inter- and intra-patient variability (25-80%), so as to maintain proper drug exposure within a therapeutic range. Etoposide posses high plasma protein binding (97%) and is degraded via complex metabolic pathways. The main pharmacokinetic determinants of etoposide are still not completely defined in order to optimize the pharmaco-therapeutic parameters including dose, therapeutic schedule and route of administration. Much research has been done to determine drug-drug and herb-drug interactions for improving the bioavailability of etoposide. The present article gives insight on pharmaceutical and pharmacological attempts made from time to time to overcome the erratic inter- and intra-patient variability for improving the bioavailability of etoposide. © 2013 Indian Academy of Sciences.

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