An Amphotericin B Derivative Equally Potent to Amphotericin B and with Increased Safety.

PLoS One 2016;11(9):e0162171. Epub 2016 Sep 28.

Instituto de Ciencias Físicas, Universidad Nacional Autónoma de México, Apartado Postal 48-3, 62251, Cuernavaca, Morelos, México.

Amphotericin B is the most potent antimycotic known to date. However due to its large collateral toxicity, its use, although long standing, had been limited. Many attempts have been made to produce derivatives with reduced collateral damage. The molecular mechanism of polyene has also been closely studied for this purpose and understanding it would contribute to the development of safe derivatives. Our study examined polyene action, including chemical synthesis, electrophysiology, pharmacology, toxicology and molecular dynamics. The results were used to support a novel Amphotericin B derivative with increased selectivity: L-histidine methyl ester of Amphotericin B. We found that this derivative has the same form of action as Amphotericin B, i.e. pore formation in the cell membrane. Its reduced dimerization in solution, when compared to Amphotericin B, is at least partially responsible for its increased selectivity. Here we also present the results of preclinical tests, which show that the derivative is just as potent as Amphotericin B and has increased safety.

Download full-text PDF


Still can't find the full text of the article?

Sign up to send a request to the authors directly.
September 2016
19 Reads
2 PubMed Central Citations(source)
3.23 Impact Factor

Publication Analysis

Top Keywords

amphotericin derivative
increased safety
increased selectivity
potent amphotericin
amphotericin increased
pharmacology toxicology
electrophysiology pharmacology
toxicology molecular
dynamics support
derivative increased
novel amphotericin
support novel
synthesis electrophysiology
molecular dynamics
polyene action
safe derivatives
development safe
contribute development
understanding contribute


(Supplied by CrossRef)
Polyene antibiotic–sterol interactions in membranes of Acholeplasmalaidlawii cells and lecithin liposomes. 3. Molecular structure of the polyene antibiotic–cholesterol complexes
B De Kruijff et al.
Biochim Biophys Acta 1974

Similar Publications

A case of large deep fibrolipoma in the left subclavicular region that compromised the branchial plexus and thoracic duct: A case report.

Int J Surg Case Rep 2018 7;48:139-141. Epub 2018 Jun 7.

ENT Department, Al- Farwaniya Institute, Kuwait.

Introduction: A fibrolipoma of the left subclavicular region, a neoplasm rarely encountered in this region, was compromising the branchial plexus and thoracic duct, causing thoracic outlet syndrome in a symptomatic patient.

Case Presentation: A 41-year-old Asian woman was brought to our ENT (ear-nose-throat) clinic because of slowly progressive swelling of the left subclavicular region since 10 years before, which became painful with time, associated with increasing subpectoral and shoulder pains, left arm swelling, and left forearm paresthesias.

Discussion: The exact etiology of fibrolipomas remains disputed, and endocrine, dysmetabolic, genetic, and traumatic factors have been often considered. Read More

View Article
June 2018
22 Reads

Turning workers into false queens: the role of exogenous pheromones in regulating reproduction in worker honey bees.

J Exp Biol 2018 Jul 10;221(Pt 13). Epub 2018 Jul 10.

Social Insects Research Group, Department of Zoology and Entomology, University of Pretoria, Private Bag X20, Hatfield 0028, Republic of South Africa.

One of the responses that honey bee workers can make in the event of queen loss is to develop into false queens. False queens are workers that exhibit both behavioural and physiological traits similar to those of a true queen. However, the presence of more than one false queen in a colony distorts the established hierarchies. Read More

View Article
July 2018
13 Reads
2.90 Impact Factor

at the interface between intermediary metabolism and oncogenesis.

World J Biol Chem 2017 Nov;8(4):175-186

Department of Chemical and Physical Biology, Centro de Investigaciones Biológicas (CSIC), Madrid 28040, Spain.

PDRG1 is a small oncogenic protein of 133 residues. In normal human tissues, the p53 and DNA damage-regulated gene 1 () gene exhibits maximal expression in the testis and minimal levels in the liver. Increased expression has been detected in several tumor cells and in response to genotoxic stress. Read More

View Article
November 2017
9 Reads

Effects of a Fragmented View of One's Partner on Interpersonal Coordination in Dance.

Front Psychol 2016 2;7:614. Epub 2016 May 2.

Donders Institute for Brain, Cognition and Behavior - Donders Centre for Cognition, Radboud University Nijmegen Nijmegen, Netherlands.

In this study we investigated the effects of a mirror-mediated, partial view of one's dance partner on interpersonal coordination in dance duets. Fourteen participant pairs (dyads) were asked to perform a reflectionally-symmetric eight-segment dance-relevant arm movement sequence in two visual conditions: with one dancer facing the mirror and providing a partial view on the dance partner, or both dancers facing back to back with, for both dancers, no view on one's partner. During an eight-count beat-preparation phase, the task was paced via a metronome at three TEMPI; 1. Read More

View Article
May 2016
12 Reads
2 PubMed Central Citations(source)

Characterization and performance of immobilized amylase and cellulase.

Appl Biochem Biotechnol 2004 ;113-116:251-9

Department of Chemical Engineering and Applied Chemistry, University of Toronto, 200 College Street, Toronto, Ontario, Canada M5S 3E5.

The performance of cellulase and amylase immobilized on siliceous supports was investigated. Enzyme uptake onto the support depended on the enzyme source and immobilization conditions. For amylase, the uptake ranged between 20 and 60%, and for cellulase, 7-10%. Read More

View Article
July 2004
12 Reads
1.74 Impact Factor