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Krishnamurthy, Chandra Kiran B.
Alternative names
Publications (4 of 4) Show all publications
Good, J. A. D., Silver, J., Nunez-Otero, C., Bahnan, W., Krishnan, K. S., Salin, O., . . . Almqvist, F. (2016). Thiazolino 2-Pyridone Amide Inhibitors of Chlamydia trachomatis Infectivity. Journal of Medicinal Chemistry, 59(5), 2094-2108
Open this publication in new window or tab >>Thiazolino 2-Pyridone Amide Inhibitors of Chlamydia trachomatis Infectivity
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2016 (English)In: Journal of Medicinal Chemistry, ISSN 0022-2623, E-ISSN 1520-4804, Vol. 59, no 5, p. 2094-2108Article in journal (Refereed) Published
Abstract [en]

The bacterial pathogen Chlamydia trachomatis is a global health burden currently treated with broad-spectrum antibiotics which disrupt commensal bacteria. We recently identified a compound through phenotypic screening that blocked infectivity of this intracellular pathogen without host cell toxicity (compound 1, KSK 120). Herein, we present the optimization of 1 to a class of thiazolino 2-pyridone amides that are highly efficacious (EC50 <= 100 nM) in attenuating infectivity across multiple serovars of C. trachomatis without host cell toxicity. The lead compound 21a exhibits reduced lipophilicity versus 1 and did not affect the growth or viability of representative commensal flora at 50 mu M. In microscopy studies, a highly active fluorescent analogue 37 localized inside the parasitiphorous inclusion, indicative of a specific targeting of bacterial components. In summary, we present a class of small molecules to enable the development of specific treatments for C. trachomatis.

Place, publisher, year, edition, pages
American Chemical Society (ACS), 2016
National Category
Microbiology in the medical area Biochemistry and Molecular Biology
Identifiers
urn:nbn:se:umu:diva-119066 (URN)10.1021/acs.jmedchem.5b01759 (DOI)000372043400031 ()26849778 (PubMedID)
Available from: 2016-04-20 Created: 2016-04-11 Last updated: 2018-06-07Bibliographically approved
Cioffi, F., Lall, U., Rus, E. & Krishnamurthy, C. K. (2015). Space-time structure of extreme precipitation in Europe over the last century. International Journal of Climatology, 35(8), 1749-1760
Open this publication in new window or tab >>Space-time structure of extreme precipitation in Europe over the last century
2015 (English)In: International Journal of Climatology, ISSN 0899-8418, E-ISSN 1097-0088, Vol. 35, no 8, p. 1749-1760Article in journal (Refereed) Published
Abstract [en]

We investigate the space-time structure of extreme precipitation in Europe over the last century, using daily rainfall data from the European Climate Assessment & Dataset (ECA&D) archive. The database includes 267 stations with records longer than 100 years. In the winter season (October to March), for each station, two classes of daily rainfall amount values are selected that, respectively, exceed the 90th and 95th percentile of daily rainfall amount over all the 100 years. For each class, and at each location, an annual time series of the frequency of exceedance and of the total precipitation, defined respectively as the number of days the rainfall threshold (90th and 95th percentiles) is exceeded and total precipitation on days when the percentile is exceeded, are developed. Space-time structure of the frequency and total precipitation time series at the different locations are then pursued using multivariate time and frequency domain methods. The identified key trends and organized spectral modes are linked to well-known climate indices, as North Atlantic Oscillation (NAO) and El Nino Southern Oscillation (ENSO). The spectra of the leading principal component of frequency of exceedance and of total precipitation have a peak with a 5-year period that is significant at the 5% level. These are also significantly correlated with ENSO series with this period. The spectrum of total rainfall is significant at the 10% level with a period of similar to 8 years. This appears to be significantly correlated to the NAO index at this period. Thus, a decomposition of both secular trends and quasi-periodic behaviour in extreme daily rainfall is provided.

Keywords
extreme precipitation, hydrology, frequency analysis, atmospheric teleconnections
National Category
Meteorology and Atmospheric Sciences
Identifiers
urn:nbn:se:umu:diva-120319 (URN)10.1002/joc.4116 (DOI)000357737000004 ()
Available from: 2016-05-16 Created: 2016-05-16 Last updated: 2018-06-07Bibliographically approved
Krishnan, K. S., Bengtsson, C., Good, J. A. D., Mirkhanov, S., Chorell, E., Johansson, L.-Å. B. -. & Almqvist, F. (2013). Synthesis of fluorescent ring-fused 2-pyridone peptidomimetics. Journal of Organic Chemistry, 78(23), 12207-12213
Open this publication in new window or tab >>Synthesis of fluorescent ring-fused 2-pyridone peptidomimetics
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2013 (English)In: Journal of Organic Chemistry, ISSN 0022-3263, E-ISSN 1520-6904, Vol. 78, no 23, p. 12207-12213Article in journal (Refereed) Published
Abstract [en]

Thiazolino fused 2-pyridones peptidomimetics are of significant biological importance due to their ability to interfere with adhesive fiber formation in uropathogenic Escherichia coli and oligomerization of amyloid fibres. We have developed an efficient synthetic route to fluorescent BODIPY analogues, with structural diversification from a key intermediate enabling introduction of C-2 substituents and late incorporation of the BODIPY moiety. A mild lithium halide mediated hydrolysis enabled preparation of peptidomimetic fluorophores with useful photophysical properties for further chemical biology applications.

Place, publisher, year, edition, pages
American Chemical Society (ACS), 2013
National Category
Chemical Sciences
Identifiers
urn:nbn:se:umu:diva-82342 (URN)10.1021/jo401844y (DOI)000328231600062 ()24161000 (PubMedID)
Funder
Swedish Research Council, 621-2010-4730
Available from: 2013-10-30 Created: 2013-10-30 Last updated: 2018-06-08Bibliographically approved
Sellstedt, M., Prasad, G. K., Krishnan, K. S. & Almqvist, F. (2012). Directed diversity-oriented synthesis. Ring-fused 5- to 10-membered rings from a common peptidomimetic 2-pyridone precursor.. Tetrahedron Letters, 53(45), 6022-6024
Open this publication in new window or tab >>Directed diversity-oriented synthesis. Ring-fused 5- to 10-membered rings from a common peptidomimetic 2-pyridone precursor.
2012 (English)In: Tetrahedron Letters, ISSN 0040-4039, E-ISSN 1359-8562, Vol. 53, no 45, p. 6022-6024Article in journal (Refereed) Published
Abstract [en]

A variety of ring-fused 2-pyridone-based central fragments were prepared using a strategy inspired by diversity-oriented synthesis. The produced compounds are diverse, yet focused, analogs of biologically active peptidomimetic 2-pyridones.

Place, publisher, year, edition, pages
Elsevier, 2012
Keywords
Diversity-oriented synthesis, Medium-sized rings, Peptidomimetics, 2-Pyridone
National Category
Chemical Sciences
Identifiers
urn:nbn:se:umu:diva-58566 (URN)10.1016/j.tetlet.2012.08.100 (DOI)
Available from: 2012-09-03 Created: 2012-09-03 Last updated: 2018-06-08Bibliographically approved
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