Rifamycins. XLI.<sup>1</sup> A New Class of Active Semisynthetic Rifamycins. N-Substituted Aminomethyl Derivatives of Rifamycin SV<sup>2</sup>

Maggi, N; Arioli, V.; Sensi, P

doi:10.1021/jm00330a013

Cited by 27 publications

(7 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Rifamycins were first discovered in 1957 as a complex antibacterial mixture of several compounds isolated from an actinomycete that was originally classified as Streptomyces mediterranei , reclassified as Nocardia mediterranea in 1969, and finally designated in 1986 as Amycolatopsis mediterranei , a newly defined genus . The only product isolated in pure crystalline form from the mixture as a minor component was rifamycin B ( 44 ).…”

Section: Microbial Metabolitesmentioning

confidence: 99%

New Horizons for Old Drugs and Drug Leads

2014

View full text Add to dashboard Cite

There is mounting urgency to find new drugs for the treatment of serious infectious diseases and cancer that are rapidly developing resistance to previously effective drugs. One approach to addressing this need is through drug repurposing, which refers to the discovery of new useful activities for "old" clinically used drugs through screening them against relevant disease targets. A large number of potential drug that, for various reasons, have failed to advance to clinical and commercial use can be added to the candidates available for such purposes. The application of new techniques and methodology developed through the impressive progress made in multidisciplinary, natural product-related research in recent years should aid substantially in expediting the discovery and development process. This review briefly outlines some of these developments as applied to a number of selected natural product examples, which may also include advances in chemical synthesis of derivatives with extended biological activities.

show abstract

Section: Microbial Metabolitesmentioning

confidence: 99%

New Horizons for Old Drugs and Drug Leads

2014

View full text Add to dashboard Cite

show abstract

“…When RFP is orally administered, the major metabolite detected in urine is 25-desacetylrifampicin (DA-RFP) [15], with about 30% of unchanged RFP excreted in urine. The anti-tubercle bacillus activity of DA-RFP is reported to be lower than RFP [16,17]. Thus, it is important to develop an administration method to efficiently deliver unmetabolized RFP to the lungs.…”

Section: Introductionmentioning

confidence: 99%

The behavior of PLGA microspheres containing rifampicin in alveolar macrophages

Onoshita

Shimizu

Yamaya

et al. 2010

Colloids and Surfaces B: Biointerfaces

View full text Add to dashboard Cite

“…The spectral changes were shown to be specific for the oxidation of rifampin and verified by mass spectrometry (MS/MS) [18]. Rifamycin SV is known to oxidize to form rifamycin S in the presence of divalent cations, a reaction used for the synthesis of rifamycin analogs [42, 43]. Rifampin and rifapentine are similar in structure and spectral characteristics.…”

Section: Discussionmentioning

confidence: 99%

Antibacterial activity of rifamycins for M. smegmatis with comparison of oxidation and binding to tear lipocalin

Staudinger

Redl

Glasgow

2014

Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics

View full text Add to dashboard Cite

A mutant of Mycobacterium smegmatis is a potential class I model substitute for Mycobacterium tuberculosis. Because not all of the rifamycins have been tested in this organism, we determined bactericidal profiles for the 6 major rifamycin derivatives. The profiles closely mirrored that established for Mycobacterium tuberculosis. Rifalazil was confirmed to be the most potent rifamycin. Because the tuberculous granuloma presents a harshly oxidizing environment we explored the effects of oxidation on rifamycins. Mass spectrometry confirmed that three of the six major rifamycins showed autoxidation in the presence of trace metals. Oxidation could be monitored by distinctive changes including isosbestic points in the ultraviolet-visible spectrum. Oxidation of rifamycins abrogated antimycobacterial activity in Mycobacterium smegmatis. Protection from autoxidation was conferred by binding susceptible rifamycins to tear lipocalin, a promiscuous lipophilic protein. Rifalazil was not susceptible to autoxidation but was insoluble in aqueous. Solubility was enhanced when complexed to tear lipocalin and was accompanied by a spectral red shift. The positive solvatochromism was consistent with robust molecular interaction and binding. Other rifamycins also formed a complex with lipocalin, albeit to a lesser extent. Protection from oxidation and enhancement of solubility with protein binding may have implications for delivery of select rifamycin derivatives.

show abstract

Rifamycins. XLI.¹ A New Class of Active Semisynthetic Rifamycins. N-Substituted Aminomethyl Derivatives of Rifamycin SV²

Cited by 27 publications

References 0 publications

New Horizons for Old Drugs and Drug Leads

New Horizons for Old Drugs and Drug Leads

The behavior of PLGA microspheres containing rifampicin in alveolar macrophages

Antibacterial activity of rifamycins for M. smegmatis with comparison of oxidation and binding to tear lipocalin

Contact Info

Product

Resources

About

Rifamycins. XLI.1 A New Class of Active Semisynthetic Rifamycins. N-Substituted Aminomethyl Derivatives of Rifamycin SV2

Cited by 27 publications

References 0 publications

New Horizons for Old Drugs and Drug Leads

New Horizons for Old Drugs and Drug Leads

The behavior of PLGA microspheres containing rifampicin in alveolar macrophages

Antibacterial activity of rifamycins for M. smegmatis with comparison of oxidation and binding to tear lipocalin

Contact Info

Product

Resources

About

Rifamycins. XLI.¹ A New Class of Active Semisynthetic Rifamycins. N-Substituted Aminomethyl Derivatives of Rifamycin SV²