8 research outputs found

    Quinoline Heterocycles: Synthesis and Bioactivity

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    Among heterocyclic compounds, quinoline is a privileged scaffold that appears as an important construction motif for the development of new drugs. Quinoline nucleus is endowed with a variety of therapeutic activities, and new quinolone derivatives are known to be biologically active compounds possessing several pharmacological activities. Many new therapeutic agents have been developed by using quinoline nucleus. Hence, quinoline and its derivatives form an important class of heterocyclic compounds for the new drug development. Numerous synthetic routes have been developed for the synthesis of quinoline and its derivatives due to its wide range of biological and pharmacological activities. The article covers the synthesis as well as biological activities of quinoline derivatives such as antimalarial, anticancer, antibacterial, anthelmintic, antiviral, antifungal, anti-inflammatory, analgesic, cardiovascular, central nervous system, hypoglycemic, and miscellaneous activities

    Databases and QSAR for Cancer Research

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    In this review, we take a survey of bioinformatics databases and quantitative structure-activity relationship studies reported in published literature. Databases from the most general to special cancer-related ones have been included. Most commonly used methods of structure-based analysis of molecules have been reviewed, along with some case studies where they have been used in cancer research. This article is expected to be of use for general bioinformatics researchers interested in cancer and will also provide an update to those who have been actively pursuing this field of research

    Synthesis and Molecular Modeling Studies of Bicyclic Inhibitors of Dihydrofolate Reductase, Receptor Tyrosine Kinases and Tubulin

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    The results from this work are reported into two sections listed below: Synthesis: Following structural classes of compounds have been designed, synthesized and studied as inhibitors of pjDHFR, RTKs and tubulin: 1. 2,4-Diamino-6-(substituted-arylmethyl)pyrido[2,3-d]pyrimidines 2. 4-((3-Bromophenyl)linked)-6-(substituted-benzyl)-7H-pyrrolo[2,3-d]pyrimidin-2-amines 3. 6-Methyl-5-((substitutedphenyl)thio)-7H-pyrrolo[2,3-d]pyrimidin-2-amines A total of 35 new compounds (excluding intermediates) were synthesized, characterized and submitted for biological evaluation. Results from these studies will be presented in due course. Bulk synthesis of the potent lead compound 170 was carried out to facilitate in vivo evaluation. Docking Studies Docking studies were performed using LeadIT, MOE, Sybyl or Flexx for target compounds listed above and for other compounds reported by Gangjee et al. against the following targets: 1. Dihydrofolate reductase: human, P. carinii, P. jirovecii (pjDHFR) and T. gondii (tgDHFR) 2. Thymidylate synthase: human (hTS) and T. gondii (tgTS) 3. Receptor tyrosine kinases: VEGFR2, EGFR and PDGFR-ÎČ 4. Colchicine binding site of tublulin. Novel homology models were generated and validated for pjDHFR, tgDHFR, tgTS, PDGFR-ÎČ and the F36C L65P pjDHFR double mutant. The tgTS homology model generated in this study and employed to design novel inhibitors shows remarkable similarity with the recently published X-ray crystal structures. Docking studies were performed to provide a molecular basis for the observed activity of target compounds against DHFR, RTKs or tubulin. Results from these studies support structure-based and ligand-based medicinal chemistry efforts in order to improve potency and/or selectivity of analogs of the docked compounds against these targets. Novel topomer CoMFA models were developed for tgTS and hTS using a set of 85 bicyclic inhibitors and for RTKs using a set of 60 inhibitors reported by Gangjee et al. The resultant models could be used to explain the potency and/or selectivity differences for selected molecules for tgTS over hTS. Topomer CoMFA maps show differences in steric and/or electronic requirements among the three RTKs, and could be used, in conjuction with other medicinal chemistry approaches, to modulate the selectivity and/or potency of inhibitors with multiple RTK inhibitory potential. Drug design efforts that involve virtual library screening using these topomer CoMFA models in conjunction with traditional medicinal chemistry techniques and docking are currently underway

    Heterocycles

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    Heterocycles have constituted the largest area of research in organic chemistry. These heterocycles play an important role in biochemical processes because the side groups of the most typical and essential constituents of living cells, DNA and RNA, are based on aromatic heterocycles. Many synthetic methods have been developed for the preparation of heterocycles. The recent surge of interest in the chemistry of heterocycles can be explained by their unusual properties and exotic structure. These heterocycles include highly stable aromatic compounds that display physicochemical properties with relevance in the design of new materials. Thus, heterocycles contribute to the development of society from a biological and industrial point of view

    Design, synthesis and biological evaluation of pyrazolo-pyrimidines and related isosteres as inhibitors of protein kinases, potential antineoplastic agents

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    Design, synthesis and biological evaluation of pyrazolo-pyrimidines and related isosteres as inhibitors of protein kinases, potential antineoplastic agent
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