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  • 1. Aeluri, Madhu
    et al.
    Gaddam, Jagan
    Trinath, Devarakonda V. K. S.
    Chandrasekar, Gayathri
    Södertörn University, School of Natural Sciences, Technology and Environmental Studies.
    Kitambi, Satish Srinivas
    Södertörn University, School of Natural Sciences, Technology and Environmental Studies. Karolinska institutet.
    Arya, Prabhat
    An Intramolecular Heck Approach To Obtain 17-Membered Macrocyclic Diversity and the Identification of an Antiangiogenesis Agent from a Zebrafish Assay2013In: European Journal of Organic Chemistry, ISSN 1434-193X, E-ISSN 1099-0690, no 19, p. 3955-3958Article in journal (Refereed)
    Abstract [en]

    We report a practical and modular approach to obtain two different types of 17-membered ring macrocyclic compounds through an intramolecular Heck reaction. These macrocyclic compounds are functionalized, that is, they contain two contiguous stereogenic hydroxy functional groups and an amino acid moiety in the macrocyclic ring skeleton. The macrocycles were then screened against a zebrafish assay to determine the antiangiogenesis activity of these small molecules. Macrocyclic compound 2.2a was identified as a potent inhibitor at 2.5 M, whereas its acyclic precursor and the other related macrocyclic compounds did not show any effect.

  • 2. Aeluri, Madhu
    et al.
    Pramanik, Chinmoy
    Chetia, Lakshindra
    Mallurwar, Naveen Kumar
    Balasubramanian, Sridhar
    Chandrasekar, Gayathri
    Södertörn University, School of Natural Sciences, Technology and Environmental Studies.
    Kitambi, Satish Srinivas
    Södertörn University, School of Natural Sciences, Technology and Environmental Studies. Karolinska Institute.
    Arya, Prabhat
    14-Membered Macrocyclic Ring-Derived Toolbox: The Identification of Small Molecule Inhibitors of Angiogenesis and Early Embryo Development in Zebrafish Assay2013In: Organic Letters, ISSN 1523-7060, E-ISSN 1523-7052, Vol. 15, no 3, p. 436-439Article in journal (Other academic)
    Abstract [en]

    A highly practical and modular synthesis to obtain a diverse 14-membered ring-based macrocyclic toolbox is achieved. These compounds were further tested in zebrafish assays related to early embryonic development, angiogenesis, and neurogenesis, respectively. 1.4c was Identified as an antiangiogenesis agent.

  • 3. Chamakuri, Srinivas
    et al.
    Guduru, Shiva Krishna Reddy
    Pamu, Sreedhar
    Chandrasekar, Gayathri
    Södertörn University, School of Natural Sciences, Technology and Environmental Studies.
    Kitambi, Satish Srinivas
    Södertörn University, School of Natural Sciences, Technology and Environmental Studies. Karolinska institutet.
    Arya, Prabhat
    A Modular Approach to Build Macrocyclic Diversity in Aminoindoline Scaffolds Identifies Antiangiogenesis Agents from a Zebrafish Assay2013In: European Journal of Organic Chemistry, ISSN 1434-193X, E-ISSN 1099-0690, no 19, p. 3959-3964Article in journal (Refereed)
    Abstract [en]

    A modular approach to explore the macrocyclic chemical space around an aminoindoline scaffold is developed. This is achieved by incorporating an amino acid moiety and subsequent stitching technology. Through screening of a zebrafish assay, several antiangiogenesis agents are identified.

  • 4.
    Chandrasekar, Gayathri
    et al.
    Södertörn University, School of Life Sciences.
    Lauter, Gilbert
    Södertörn University, School of Life Sciences.
    Hauptmann, Giselbert
    Södertörn University, School of Life Sciences.
    Distribution of corticotropin-releasing hormone in the developing zebrafish brain2007In: Journal of Comparative Neurology, ISSN 0021-9967, E-ISSN 1096-9861, Vol. 505, no 4, p. 337-351Article in journal (Refereed)
    Abstract [en]

    Corticotropin-releasing hormone (CRH) plays a central role in the physiological regulation of the hypothalamus-pituitary-adrenal/interrenal axis mediating endocrine, behavioral, autonomic, and immune responses to stress. Despite the wealth of knowledge about the physiological roles of CRH, the genetic mechanisms by which CRH neurons arise during development are poorly understood. As a first step toward analyzing the molecular and genetic pathways involved in CRH lineage specification, we describe the developmental distribution of CRH neurons in the embryonic zebrafish, a model organism for functional genomics and developmental biology. We searched available zebrafish expressed sequence tag (EST) databases for CRH-like sequences and identified one EST that contained the complete zebrafish CRH open reading frame (ORF). The CRH precursor sequence contained a signal peptide, the CRH peptide, and a cryptic peptide with a conserved sequence motif. RT-PCR analysis showed crh expression in a wide range of adult tissues as well as during embryonic and larval stages. By whole-mount in situ hybridization histochemistry, discrete crh-expressing cell clusters were found in different parts of the embryonic zebrafish brain, including telencephalon, preoptic region, hypothalamus, posterior tuberculum, thalamus, epiphysis, midbrain tegmentum, and rostral hindbrain and in the neural retina. The localization of crh mRNA within the preoptic region is consistent with the central role of CRH in the teleost stress response through activation of the hypothalamic-pituitary-interrenal axis. The widespread distribution of CRH-synthesizing cells outside the preoptic region suggests additional functions of CRH in the embryonic zebrafish brain.

  • 5. Dasari, Bhanudas
    et al.
    Jogula, Srinivas
    Borhade, Ramdas
    Balasubramanian, Sridhar
    Chandrasekar, Gayathri
    Södertörn University, School of Natural Sciences, Technology and Environmental Studies.
    Kitambi, Satish Srinivas
    Södertörn University, School of Natural Sciences, Technology and Environmental Studies. Karolinska Institute.
    Arya, Prabhat
    Macrocyclic Glycohybrid Toolbox Identifies Novel Antiangiogenesis Agents from Zebrafish Assay2013In: Organic Letters, ISSN 1523-7060, E-ISSN 1523-7052, Vol. 15, no 3, p. 432-435Article in journal (Other academic)
    Abstract [en]

    A practical and modular approach to obtain a diverse set of 14-membered macrocyclic compounds from carbohydrates is developed that utilizes functional groups at C-1 and C-5. The evaluation of this toolbox in various zebrafish assays led to the identification of 2.7f as an antianglogenesis agent.

  • 6. Guduru, Shiva Krishna Reddy
    et al.
    Chamakuri, Srinivas
    Chandrasekar, Gayathri
    Södertörn University, School of Natural Sciences, Technology and Environmental Studies.
    Kitambi, Satish Srinivas
    Södertörn University, School of Natural Sciences, Technology and Environmental Studies. Karolinska Institutet.
    Arya, Prabhat
    Tetrahydroquinoline-Derived Macrocyclic Toolbox: The Discovery of Antiangiogenesis Agents in Zebrafish Assay2013In: ACS Medicinal Chemistry Letters, ISSN 1948-5875, E-ISSN 1948-5875, Vol. 4, no 7, p. 666-670Article in journal (Refereed)
    Abstract [en]

    A novel approach to incorporate the macrocyclic rings onto the privileged substructure, i.e. tetrahydroquinoline scaffold, is developed. The presence of an amino acid-derived moiety in the macrocyclic skeleton provides an opportunity to modulate the nature of the chiral side chain. Further, evaluation in a zebrafish screen identified three active small molecules (2.5b, 3.2d, and 4.2) as antiangiogenesis agents at 2.5 mu M.

  • 7.
    Kitambi, Satish Srinivas
    et al.
    Södertörn University, School of Life Sciences. Karolinska Institute.
    Chandrasekar, Gayathri
    Södertörn University, School of Life Sciences. Karolinska Institute.
    Addanki, Vamsi Krishna
    Teleost fish - Powerful models for studying development, function and diseases of the human eye2011In: Current Science, ISSN 0011-3891, Vol. 100, no 12, p. 1815-1823Article in journal (Refereed)
    Abstract [en]

    The human eye is a highly specialized structure and defects in its development or functioning process have an impact on the quality of life. Different animal models, especially murine models, have been used to identify the key molecular players required for the normal functioning of the eye. This review highlights the importance of the teleost model in dissecting the development, functioning process and diseases of the human eye. A high degree of conservation is seen in the development, organization and function of the eye throughout vertebrates. Vertebrate teleost models, zebrafish and medaka, have become popular to study various aspects of developmental biology and genetics. Teleost eye shows high similarity to that of the mammalian eye; for example, as seen in mammals, the retina of zebrafish and medaka shows six types of neurons and one type of glia arranged in three layers. In addition, rapid embryonic development, transparency during early development, and the availability of various biochemical, molecular and genetic techniques applicable on these models facilitate in dissecting the developmental and functioning processes of the eye. The availability of mutants with eye defects in zebrafish and medaka allows the possibility of utilizing these two species as comparative models in gaining rapid understanding of the developmental events of various human diseases. The small size of these fish embryos and their availability in large numbers allow performing medically relevant chemical screens to identify potential drug and/or drug targets for different human eye conditions.

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