Synthesis, in vitro, and in vivo antibacterial activity of nocathiacin I thiol-Michael adducts

Naidu, B. Narasimhulu; Sorenson, Margaret E.; Bronson, Joanne J.; Pucci, Michael J.; Clark, Junius M.; Ueda, Yasutsugu

doi:10.1016/j.bmcl.2005.02.046

Cited by 48 publications

(24 citation statements)

References 16 publications

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“…Due to the promising antibacterial activity of nocathiacins and to the presence of several functional groups in their structure suitable for chemical manipulation, some research groups reported the semi-synthetic derivatives of these natural products in order to improve aqueous solubility while maintaining the intrinsic biological activity [93,94]. Representative N- hydroxyindole scaffold-based semi-synthetic products 49a-c in Table 2 were obtained by the addition of amines to the dehydroalanine side chain of nocathiacin I, in particular primary, secondary and cyclic amines with different functional groups were inserted to create analogues of nocathiacin I.…”

Section: N-hydroxy-substituted Fused Five-membered Ring Systemsmentioning

confidence: 99%

Bioactive heterocycles containing endocyclic N-hydroxy groups

Rani

Granchi

2015

European Journal of Medicinal Chemistry

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Drug-likeness rules consider N-O single bonds as “structural alerts” which should not be present in a perspective drug candidate. In most cases this concern is correct, since it is known that N-hydroxy metabolites of branded drugs produce reactive species that cause serious side effects. However, this dangerous reactivity of the N-OH species generally takes place when the nitrogen atom is not comprised in a cyclic moiety. In fact, the same type of metabolic behavior should not be expected when the nitrogen atom is included in the ring of an aromatic heterocyclic scaffold. Nevertheless, heterocycles bearing endocyclic N-hydroxy portions have so far been poorly studied as chemical classes that may provide new therapeutic agents. This review provides an overview of N-OH-containing heterocycles with reported bioactivities that may be considered as therapeutically relevant and, therefore, may extend the chemical space available for the future development of novel pharmaceuticals. A systematic treatment of the various chemical classes belonging to this particular family of molecules is described along with a discussion of the biological activities associated to the most important examples.

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Section: N-hydroxy-substituted Fused Five-membered Ring Systemsmentioning

confidence: 99%

Bioactive heterocycles containing endocyclic N-hydroxy groups

Rani

Granchi

2015

European Journal of Medicinal Chemistry

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“…Promising sites for the requisite semisynthetic modification [15] of 1 could be the dehydroalanine Michael acceptors. [16] We found that cropping of the dehydroamino acid tail [17,18] of 1 was crucial to allow clean transformations.…”

mentioning

confidence: 99%

A Fluorescent Probe for the 70 S‐Ribosomal GTPase‐Associated Center

et al. 2009

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“…Solvent was pumped from the top using a FMI pump. The column was eluted with two column volumes each of 1:4 hexane-DCM (fraction 3) and 2.5% MeOH-DCM (fractions 4-6), 1.5 column volume of 5% MeOH-DCM(fractions7-11),onecolumnvolumeof10%MeOH-DCM (fractions [12][13][14][15], and 1.5 column volumes each of 20% (fraction [16][17][18], 50% (19)(20)(21), and finally 100% MeOH. Fractions were pooled based on TLC analysis and analytical HPLC, affording fractions 1-24 as listed in parentheses with the elution solvents.…”

Section: Methodsmentioning

confidence: 99%

Thiazomycins, Thiazolyl Peptide Antibiotics from Amycolatopsis fastidiosa

et al. 2009

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Thiazolyl peptides are a class of highly rigid trimacrocyclic compounds consisting of varying but large numbers of thiazole rings. The need for new antibacterial agents to treat infections caused by resistant bacteria prompted a reinvestigation of this class, leading to the previous isolation of thiazolyl peptides, namely, thiazomycin (5) and thiazomycin A (6), congeners of nocathiacins (1-4). Continued chemical screening led to the isolation of six new thiazolyl peptide congeners (8-13), of which three had truncated structures lacking an indole residue. From these, compound 8 showed activity similar to thiazomycin. Two compounds (9 and 10) showed intermediate activities, and the three truncated compounds (11-13) were essentially inactive. The discovery of the truncated compounds revealed the minimal structural requirements for activity and suggested probable biosynthetic pathways for more advanced compounds. The isolation, structure elucidation, antibacterial activity, and proposed biogenesis of thiazomycins are herein described.

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Synthesis, in vitro, and in vivo antibacterial activity of nocathiacin I thiol-Michael adducts

Cited by 48 publications

References 16 publications

Bioactive heterocycles containing endocyclic N-hydroxy groups

Bioactive heterocycles containing endocyclic N-hydroxy groups

A Fluorescent Probe for the 70 S‐Ribosomal GTPase‐Associated Center

Thiazomycins, Thiazolyl Peptide Antibiotics from Amycolatopsis fastidiosa

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