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Kitambi, Satish Srinivas
Alternative names
Publications (10 of 15) Show all publications
Aeluri, M., Pramanik, C., Chetia, L., Mallurwar, N. K., Balasubramanian, S., Chandrasekar, G., . . . Arya, P. (2013). 14-Membered Macrocyclic Ring-Derived Toolbox: The Identification of Small Molecule Inhibitors of Angiogenesis and Early Embryo Development in Zebrafish Assay. Organic Letters, 15(3), 436-439
Open this publication in new window or tab >>14-Membered Macrocyclic Ring-Derived Toolbox: The Identification of Small Molecule Inhibitors of Angiogenesis and Early Embryo Development in Zebrafish Assay
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2013 (English)In: Organic Letters, ISSN 1523-7060, E-ISSN 1523-7052, Vol. 15, no 3, p. 436-439Article in journal (Other academic) Published
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.

National Category
Organic Chemistry
Identifiers
urn:nbn:se:sh:diva-19440 (URN)10.1021/ol3032126 (DOI)000314559000003 ()2-s2.0-84873370245 (Scopus ID)
Available from: 2013-07-11 Created: 2013-07-11 Last updated: 2017-12-06Bibliographically approved
Chamakuri, S., Guduru, S. K., Pamu, S., Chandrasekar, G., Kitambi, S. S. & Arya, P. (2013). A Modular Approach to Build Macrocyclic Diversity in Aminoindoline Scaffolds Identifies Antiangiogenesis Agents from a Zebrafish Assay. European Journal of Organic Chemistry (19), 3959-3964
Open this publication in new window or tab >>A Modular Approach to Build Macrocyclic Diversity in Aminoindoline Scaffolds Identifies Antiangiogenesis Agents from a Zebrafish Assay
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2013 (English)In: European Journal of Organic Chemistry, ISSN 1434-193X, E-ISSN 1099-0690, no 19, p. 3959-3964Article in journal (Refereed) Published
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.

National Category
Biochemistry and Molecular Biology
Identifiers
urn:nbn:se:sh:diva-19538 (URN)10.1002/ejoc.201300409 (DOI)000320720100003 ()2-s2.0-8487919808 (Scopus ID)
Available from: 2013-08-22 Created: 2013-08-20 Last updated: 2017-12-06Bibliographically approved
Aeluri, M., Gaddam, J., Trinath, D. V. K., Chandrasekar, G., Kitambi, S. S. & Arya, P. (2013). An Intramolecular Heck Approach To Obtain 17-Membered Macrocyclic Diversity and the Identification of an Antiangiogenesis Agent from a Zebrafish Assay. European Journal of Organic Chemistry (19), 3955-3958
Open this publication in new window or tab >>An Intramolecular Heck Approach To Obtain 17-Membered Macrocyclic Diversity and the Identification of an Antiangiogenesis Agent from a Zebrafish Assay
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2013 (English)In: European Journal of Organic Chemistry, ISSN 1434-193X, E-ISSN 1099-0690, no 19, p. 3955-3958Article in journal (Refereed) Published
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.

National Category
Chemical Sciences
Identifiers
urn:nbn:se:sh:diva-19539 (URN)10.1002/ejoc.201300408 (DOI)000320720100002 ()2-s2.0-84879246191 (Scopus ID)
Available from: 2013-08-22 Created: 2013-08-20 Last updated: 2017-12-06Bibliographically approved
Jogula, S., Dasari, B., Khatravath, M., Chandrasekar, G., Kitambi, S. S. & Arya, P. (2013). Building a Macrocyclic Toolbox from C-Linked Carbohydrates Identifies Antiangiogenesis Agents from Zebrafish Assay. European Journal of Organic Chemistry, 2013(23), 5036-5040
Open this publication in new window or tab >>Building a Macrocyclic Toolbox from C-Linked Carbohydrates Identifies Antiangiogenesis Agents from Zebrafish Assay
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2013 (English)In: European Journal of Organic Chemistry, ISSN 1434-193X, E-ISSN 1099-0690, Vol. 2013, no 23, p. 5036-5040Article in journal (Refereed) Published
Abstract [en]

We report the synthesis of four different types of macrocyclic-derived glycohybrids from carbohydrates that have an amino acid moiety in the large-ring skeleton. These macrocyclic glycohybrids were obtained from -C-1H- and -C-1H-linked carbohydrates. In one series, we utilized ring-closing metathesis as the stitching technology to obtain two different macrocycles, i.e., trans equatorial-axial C-1H and C-5H and cis axial-axial C-1H and C-5H. The click approach was the key reaction in our second series to obtain two other macrocyclic compounds, i.e., trans equatorial-axial C-1H and C-5H and cis axial-axial C-1H and C-5H. The evaluation of this toolbox resulted in the identification of two unique compounds as antiangiogenesis agents in an embryonic zebrafish assay. Interestingly, in both cases, the macrocyclic compounds that have a cis relationship (i.e., axial-axial orientation) between C-1H and C-5H showed activity and their other diastereomers (i.e., equatorial-axial C-1H and C-5 H) with a trans relationship did not show any effect.

National Category
Chemical Sciences
Identifiers
urn:nbn:se:sh:diva-19664 (URN)10.1002/ejoc.201300548 (DOI)000322761000008 ()2-s2.0-84885953757 (Scopus ID)
Available from: 2013-09-06 Created: 2013-09-06 Last updated: 2017-12-06Bibliographically approved
Dasari, B., Jogula, S., Borhade, R., Balasubramanian, S., Chandrasekar, G., Kitambi, S. S. & Arya, P. (2013). Macrocyclic Glycohybrid Toolbox Identifies Novel Antiangiogenesis Agents from Zebrafish Assay. Organic Letters, 15(3), 432-435
Open this publication in new window or tab >>Macrocyclic Glycohybrid Toolbox Identifies Novel Antiangiogenesis Agents from Zebrafish Assay
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2013 (English)In: Organic Letters, ISSN 1523-7060, E-ISSN 1523-7052, Vol. 15, no 3, p. 432-435Article in journal (Other academic) Published
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.

National Category
Organic Chemistry
Identifiers
urn:nbn:se:sh:diva-19439 (URN)10.1021/ol3032297 (DOI)000314559000002 ()2-s2.0-84873368544 (Scopus ID)
Available from: 2013-07-11 Created: 2013-07-11 Last updated: 2017-12-06Bibliographically approved
Guduru, S. K., Chamakuri, S., Chandrasekar, G., Kitambi, S. S. & Arya, P. (2013). Tetrahydroquinoline-Derived Macrocyclic Toolbox: The Discovery of Antiangiogenesis Agents in Zebrafish Assay. ACS Medicinal Chemistry Letters, 4(7), 666-670
Open this publication in new window or tab >>Tetrahydroquinoline-Derived Macrocyclic Toolbox: The Discovery of Antiangiogenesis Agents in Zebrafish Assay
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2013 (English)In: ACS Medicinal Chemistry Letters, ISSN 1948-5875, E-ISSN 1948-5875, Vol. 4, no 7, p. 666-670Article in journal (Refereed) Published
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.

National Category
Biochemistry and Molecular Biology
Identifiers
urn:nbn:se:sh:diva-19544 (URN)10.1021/ml400026n (DOI)000321883800022 ()24900727 (PubMedID)2-s2.0-84880142629 (Scopus ID)
Available from: 2013-08-22 Created: 2013-08-20 Last updated: 2017-07-17Bibliographically approved
Kitambi, S. S., Chandrasekar, G. & Addanki, V. K. (2011). Teleost fish - Powerful models for studying development, function and diseases of the human eye. Current Science, 100(12), 1815-1823
Open this publication in new window or tab >>Teleost fish - Powerful models for studying development, function and diseases of the human eye
2011 (English)In: Current Science, ISSN 0011-3891, Vol. 100, no 12, p. 1815-1823Article in journal (Refereed) Published
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.

Keywords
Development and functioning process, Diseases, Drug screen, Human eye, Teleost model, Animalia, Danio rerio, Mammalia, Murinae, Oryzias, Oryziinae, Teleostei, Vertebrata
National Category
Ophthalmology
Identifiers
urn:nbn:se:sh:diva-22859 (URN)000292651400018 ()2-s2.0-79960081316 (Scopus ID)
Available from: 2014-03-28 Created: 2014-03-28 Last updated: 2017-12-05Bibliographically approved
Kitambi, S. S., McCulloch, K. J., Peterson, R. T. & Malicki, J. J. (2009). Small molecule screen for compounds that affect vascular development in the zebrafish retina. Mechanisms of Development, 126(5-6), 464-477
Open this publication in new window or tab >>Small molecule screen for compounds that affect vascular development in the zebrafish retina
2009 (English)In: Mechanisms of Development, ISSN 0925-4773, E-ISSN 1872-6356, Vol. 126, no 5-6, p. 464-477Article in journal (Refereed) Published
Abstract [en]

Blood vessel formation in the vertebrate eye is a precisely regulated process. in the human retina, both an excess and a deficiency of blood vessels may lead to a loss of vision. To gain insight into the molecular basis of vessel formation in the vertebrate retina and to develop pharmacological means of manipulating this process in a living organism, we further characterized the embryonic zebrafish eye vasculature, and performed a small molecule screen for compounds that affect blood vessel morphogenesis. The screening of approximately 2000 compounds revealed four small molecules that at specific concentrations affect retinal vessel morphology but do not produce obvious changes in trunk vessels, or in the neuronal architecture of the retina. Of these, two induce a pronounced widening of vessel diameter without a substantial loss of vessel number, one compound produces a loss of retinal blood vessels accompanied by a mild increase of their diameter, and finally one other generates a severe loss of retinal vessels. This work demonstrates the utility of zebrafish as a screening tool for small molecules that affect eye vasculature and presents several compounds of potential therapeutic importance.

National Category
Developmental Biology
Identifiers
urn:nbn:se:sh:diva-13901 (URN)10.1016/j.mod.2009.01.002 (DOI)000266975100016 ()19445054 (PubMedID)2-s2.0-67349147007 (Scopus ID)
Note

Som manuskript i avhandling. As manuscript in dissertation.

Available from: 2011-12-14 Created: 2011-12-14 Last updated: 2017-07-18Bibliographically approved
Kitambi, S. S. (2009). Teleost retina: a model for study neurogenesis and angiogenesis. (Doctoral dissertation). Stockholm: Karolinska instiutet
Open this publication in new window or tab >>Teleost retina: a model for study neurogenesis and angiogenesis
2009 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Teleost models, zebrafish and medaka have become popular models to study various aspects of developmental biology and genetics. The rapid embryonic development, transparent embryos and the availability of many mutants for various developmental and molecular pathways contribute to the usefulness of these models. The availability of various biochemical, molecular and genetic techniques applicable on these models facilitate in dissecting developmental processes. Teleost retina shows very high similarity to that seen in mammalian retina. The arrangement of the six types of neurons and one type of glia is very similar. Zebrafish has been extensively used in gaining insight into the development and functioning of the retina. Medaka, on the other hand has not been so extensively capitalized as zebrafish. The current study characterizes expression of genes mainly from the nuclear receptor family and establishes the role of zebrafish liver x receptor in governing the size, patterning and neurogenesis of the retina in zebrafish. We also establish the time line of the retinal patterning of medaka retina. Zebrafish and medaka retina show both similarity and difference in the developmental events governing the patterning of the retina. In zebrafish, retinal neurogenesis follows a fan gradient pattern starting at the ventro-nasal region. In medaka, neurogenesis starts from the central retina. An additional, second domain of neurogenesis is seen with the patterning of photoreceptors in medaka. This observation highlights the possibility of utilizing these two species as comparative models in gaining rapid understanding of retinal development and function. This study also establishes the time line of vascular development in the zebrafish retina, an important event required for normal function. Similar to neurogenesis, vasculaturedevelops rapidly and this feature was utilized to develop a small molecule-screening assay. The screening resulted in identification of five compounds that produced phenotype ranging from decrease in the number of vessels to loss of vessels specifically in the retina. To gain insight into the mode of action, further analyses of three of the five identified compounds, using either morpholino knockdown or structural similarity search was done. This study highlights the advantage of using zebrafish model to perform medically relevant chemical screen.

Place, publisher, year, edition, pages
Stockholm: Karolinska instiutet, 2009. p. 37
National Category
Biological Sciences
Identifiers
urn:nbn:se:sh:diva-31551 (URN)978-91-7409-365-0 (ISBN)
Public defence
2009-03-30, Månen, Alfred Nobels allé 8, Huddinge, 09:00
Opponent
Supervisors
Available from: 2016-12-29 Created: 2016-12-29 Last updated: 2016-12-29Bibliographically approved
Kitambi, S. S. & Malicki, J. J. (2008). Spatiotemporal Features of Neurogenesis in the Retina of Medaka, Oryzias latipes. Developmental Dynamics, 237(12), 3870-3881
Open this publication in new window or tab >>Spatiotemporal Features of Neurogenesis in the Retina of Medaka, Oryzias latipes
2008 (English)In: Developmental Dynamics, ISSN 1058-8388, E-ISSN 1097-0177, Vol. 237, no 12, p. 3870-3881Article in journal (Refereed) Published
Abstract [en]

The vertebrate retina is very well conserved in evolution. Its structure and functional features are very similar in phyla as different as primates and teleost fish. Here, we describe the spatiotemporal characteristics of neurogenesis in the retina of a teleost, medaka, and compare them with other species, primarily the zebrafish. Several intriguing differences are observed between medaka and zebrafish. For example, photoreceptor differentiation in the medaka retina starts independently in two different areas, and at more advanced stages of differentiation, medaka and zebrafish retinae display obviously different patterns of the photoreceptor cell mosaic. Medaka and zebrafish evolutionary lineages are thought to have separated from each other 110 million years ago, and so the differences between these species are not unexpected, and may be exploited to gain insight into the architecture of developmental pathways. Importantly, this work highlights the benefits of using multiple teleost models in parallel to understand a developmental process.

National Category
Developmental Biology
Identifiers
urn:nbn:se:sh:diva-14114 (URN)10.1002/dvdy.21797 (DOI)000261679300038 ()2-s2.0-57149095268 (Scopus ID)
Available from: 2011-12-19 Created: 2011-12-16 Last updated: 2017-12-08Bibliographically approved
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