A new series of pyridine-containing analogues III-XXII of distamycin A and netrop sin was investigated by the molecular mechanics technique and molecular modelling. A pyridine analogue of netropsin (VII) is described, the first compound based on molecular studies, and two carbocyclic analogues of distamycin A with an N-terminal chloro- or bromoacetyl group (VIa, VIIa) were synthesized, as well as carbocyclic analogues of netropsin (VIIIb, Xb), potential carriers of alkylating elements. The potential use of VIa, VII, VIIa, VIIIb and Xb as carriers to place into the minor groove of DNA chemical groups capable of modifying DNA, is discussed.
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Molecules
November 2024
Institute of Pharmaceutical Chemistry, University of Pécs, H-7624 Pécs, Hungary.
In vitro relative cytotoxicity (IC ()/IC () of ()-3-(4'-methylbenzylidene)-4-chromanone () towards human Molt 4/C8 and CEM T-lymphocytes showed a >50-fold increase in comparison to those of the respective tetralone derivative (). On the other hand, such an increase was not observed in the analogous 4-OCH ( and ) derivatives. In order to study whether thiol reactivity-as a possible basis of the mechanism of action-correlates with the observed cytotoxicities, the kinetics of the non-enzyme catalyzed reactions with reduced glutathione (GSH) and N-acetylcysteine (NAC) of and were investigated.
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November 2024
N.D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Leninsky Prospect 47, Moscow 119991, Russia.
J Nat Prod
December 2024
Institute for Molecular Bioscience, The University of Queensland, St Lucia, QLD 4072, Australia.
A bioassay-guided chemical investigation of an Australian pasture-soil-derived sp. yielded the rare carbocyclic -polyketide kendomycin () along with a series of new analogues, goondomycins A-H (-), featuring unprecedented carbo/heterocyclic scaffolds and chromophores, with structures assigned by detailed spectroscopic analysis, chemical and biochemical transformations, and biosynthetic considerations. Goondomycins B () and F () are noteworthy in being potent motility inhibitors of heartworm microfilaria (EC 0.
View Article and Find Full Text PDFJ Pept Sci
February 2025
Department of Medicinal Chemistry, University of Kansas, Lawrence, Kansas, USA.
The melanocortin 4 receptor (MC4R) plays a critical role in satiety and energy homeostasis, and its dysregulation is implicated in numerous hyperphagic and obese disease states. Setmelanotide, a disulfide-based cyclic peptide, can rescue MC4R activity and treat obesities caused by genetic defects in MC4R signaling. But this peptide has moderate blood-brain barrier penetrance and metabolic stability, which can limit its efficacy in practice.
View Article and Find Full Text PDFAngew Chem Int Ed Engl
October 2024
Department of Chemistry, University of Oxford, Chemistry Research Laboratory, Mansfield Road, Oxford, OX1 3TA, UK.
Sulfur functional groups are ubiquitous in molecules used in the pharmaceutical and agrochemical industries, and within these collections sulfones hold a prominent position. The double aza-analogues of sulfones, sulfondiimines, offer significant potential in discovery chemistry but to date their applications have been limited by the lack of convenient synthetic routes. The existing methods mainly rely on imination of low-valent-sulfur intermediates, or the combination of pre-formed organometallic reagents and electrophilic S(VI)-functionalities.
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