Publications (7)12.06 Total impact
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Article: Synthesis and inhibition properties of a series of pyranose derivatives towards a Zn-metalloproteinase from Saccharomonospora canescens.
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ABSTRACT: The Zn-proteinase, isolated from Saccharomonospora canescens (NPS), shares many common features with thermolysin, but considerable differences are also evident, as far as the substrate recognition site is concerned. In substrates of general structure AcylAlaAlaPhe 4NA, this neutral proteinase cleaves only the arylamide bond (non-typical activity of Zn-proteinases), while thermolysin attacks the peptide bond Ala-Phe. Phosphoramidon is a powerful tight binding inhibitor for thermolysin and significantly less specific towards NPS. The K(i)-values (65 μM for NPS vs 0.034 μM for thermolysin) differ nearly 2000-folds. This implies significant differences in the specificity of the corresponding subsites. The carbohydrate moiety is supposed to accommodate in the S₁-subsite and the series of arabinopyranosides and glucopyranosides (12 compounds), which are assayed as inhibitors in a model system: NPS with SucAlaAlaPhe4NA as a substrate could be considered as mapping the S₁-subsite of NPS. Members of the series with an additional ring (3,4-epithio, 3,4-anhydro-derivatives) turned out to be reasonably good competitive inhibitors (K(i)≈0.1-0.2 mM are of the same order as the K(i) value for phosphoramidon). The structure of these compounds (8, 9, 11 and 12) seems to fit the size of the S₁-subsite and due to an appropriately oriented OH-group in addition, to protect the active site Zn(2+).Carbohydrate research 11/2010; 345(16):2343-7. · 2.03 Impact Factor -
Article: Synthesis and In-Vitro Antitumor Activity of Selected 7-Fluoro-6-(4-methyl-1-piperazinyl)-2-(thiosubstituted)-4(3H)-quinazolinones
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ABSTRACT: A new series of 7-fluoro-6-(4-methyl-1-piperazinyl)-2-(thiosubstituted)-4(3H)-quinazolinones was synthesized as potential antitumor agents by multi-step synthesis starting with the commercially available 3-chloro-4-fluoroaniline. The most promising candidate, 7-fluoro-6-(4- methyl-1-thyl-1-piperazinyl)- 2-thioethyl-4(3H)-quinazolinone (5a), was screened in 60 human cancer cells by NCI.Letters in Organic Chemistry 06/2010; 7(5):360-366. · 0.82 Impact Factor -
Article: Synthesis and properties of some 2,3‐disubstituted 6‐fluoro‐7‐(4‐methyl‐1‐piperazinyl)quinoxalines
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ABSTRACT: The 2,3-disubstituted 6-fluoro-7-(4-methyl-1-piperazinyl)-quinoxalines (3–11) were synthesized for bioassay via reaction of 1.2-diamino-4-fluoro-5-(4-methyl-1-piperazinyl)benzene (2) with the appropriate 1,2-dicarbonyl compounds. However, none of the tested compounds 3–11 showed significant in vitro activ ity against E. coli ATCC11229, S. aureus ATCC6538 and C.albicans SATCC10231.Journal of Heterocyclic Chemistry 03/2009; 37(5):1273 - 1275. · 1.22 Impact Factor -
Article: A Novel Route Towards the Synthesis of Stereospecific N-Substituted Chiral Morpholines
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ABSTRACT: In this communication a convenient and novel method for the synthesis of chiral N-substituted- (arabinopyrano)[3,4-b]morpholines of pharmacological interest from anhydro sugars is described.Letters in Organic Chemistry 05/2005; 2(4):306-308. · 0.82 Impact Factor -
Article: Synthesis of methyl ether analogues of sildenafil (Viagra) possessing tyrosinase inhibitory potential.
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ABSTRACT: The microwave-assisted synthesis and characterization of the ten new sildenafil (Viagra; 1) analogues 6-15 are described. A detailed structure-activity-relationship (SAR) study revealed that compounds 10 (= 4-ethoxy-N-hydroxy-3-(7-methoxy-1-methyl-3-propyl-1H-pyrazolo[4,3-d]pyrimidin-5-yl)benzenesulfonamide) and 12 (= S-(2-hydroxyethyl) 4-ethoxy-3-(7-methoxy-1-methyl-3-propyl-1H-pyrazolo[4,3-d]pyrimidin-5-yl)benzenesulfonothioate) are extremely potent mushroom tyrosinase inhibitors, with IC50 values (3.59 and 2.15 microM, resp.) below those of the standard inhibitors L-mimosine and kojic acid (IC50 = 3.68 and 16.67 microM, resp.). Compounds 10 and 12 are, thus, the currently most-effective inhibitors of tyrosinase, and bear great potential to be used for the treatment of various skin disorders such as hyperpigmentation, which is associated with high production of melanocytes.Chemistry & Biodiversity 05/2005; 2(4):470-6. · 1.80 Impact Factor -
Article: A convenient method for the synthesis of cyclic trithiocarbonates on carbohydrate scaffolds
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ABSTRACT: An efficient regio- and stereoselective method for the synthesis of cyclic trithiocarbonates on carbohydrate skeleton is described. A freshly prepared solution of sodium trithiocarbonate reacts with cis-oriented epoxytriflate pentoses 7-11 to yield the corresponding cyclic trithiocarbonates 12-16. Structures of all new compounds are established through MS, 1H and 13C NMR techniques.Tetrahedron Letters 01/2003; · 2.68 Impact Factor -
Article: A novel method for the synthesis of 4(3H)-quinazolinones
Tetrahedron Letters 45(17):3475-3476. · 2.68 Impact Factor
Top co-authors
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Institutions
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2010
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Bulgarian Academy of Sciences
- Institute of Organic Chemistry with Center for Phytochemistry
Sofia, Oblast Sofiya-Grad, Bulgaria
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2009
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Eberhard-Karls-Universität Tübingen
Tübingen, Baden-Wuerttemberg, Germany
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2005
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University of Karachi
- International Center for Chemical and Biological Sciences
Karachi, Sindh, Pakistan
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