If a person wants to get **technical** and bring in a lawyer .. I've condensed these few articles into one legal finding ..
THIS means ONLY maltol was .. safe ..
OUT OF ALL THOSE TESTED .. maltol .. was the ONLY one found safe.
"Maltol was mildly inhibitory"
Whereas ..
L4 strongly stimulated growth of Staphylococcus epidermidis
L1 series had only a marginal effect.
Mimosine enhanced the growth
Desferrioxamine enhanced the growth.
"Derivatives of maltol"
Basic 3-hydroxypyridin-4-ones: Potential antimalarial agents
European Journal of Medicinal Chemistry
Volume 43, Issue 5, May 2008, Pages 1035-1047
Lotfollah S. Dehkordia, Zu D. Liub and Robert C. Hiderb, ,
aSchool of Pharmacy, Isfahan University of Medical Sciences, Isfahan,
Iran
bDepartment of Pharmacy, King's College London, Franklin-Wilkins
Building, 150 Stamford Street, London SE1 9NH, UK
Received 7 December 2006; revised 11 July 2007; accepted 12 July
2007. Available online 2 August 2007.
Abstract
3-Hydroxypyridin-4-ones selectively bind iron under biological
conditions and one such compound has found application in the
treatment of thalassaemia-linked iron overload.
Related molecules have also been demonstrated to possess an
antimalarial effect at levels which are non-toxic to mammalian cells.
In an attempt to improve the efficiency of such molecules we have
investigated the effect of introducing basic nitrogen centres into 3-
hydroxypyridin-4-ones in an attempt to achieve targeting to lysosomes
and other intracellular acidic vacuoles. Several of the compounds
reported in this communication possess enhanced antimalarial activity
over that of the simple hydroxypyridinone class.
Copyright © 2007 Elsevier Masson SAS All rights reserved.
--------------------
Synthesis, Physicochemical Characterization, and Biological
Evaluation
of 2-(1‘-Hydroxyalkyl)-3-hydroxypyridin-4-ones: Novel Iron Chelators
with Enhanced pFe3+ Values†
Zu D. Liu, Hicham H. Khodr, Ding Y. Liu, Shu L. Lu, and Robert C.
Hider*
Department of Pharmacy, King's College London, 150 Stamford Street,
London SE1 8AW, U.K.
J. Med. Chem., 1999, 42 (23), pp 4814–4823
Publication Date (Web): October 28, 1999
† Abbreviations: pFe3+, the negative logarithm of the concentration
of the free iron(III) in solution, calculated for total [ligand] =
10-5 M, total [iron] = 10-6 M at pH 7.4; DFO, desferrioxamine; HPO,
hydroxypyridinone; CP20, 1,2-dimethyl-3-hydroxypyridin-4-one; CP94,
1,2-diethyl-3-hydroxypyridin-4-one; D7.4, distribution coefficient at
pH 7.4; MOPS, 4-morpholinopropanesulfonic acid;
* Corresponding author: Robert C. Hider. Tel: 20 7848 4646. Fax:
20 7848 4195. E-mail: robert.hi...@kcl.ac.uk.
Abstract
The synthesis of a range of 2-(1‘-hydroxyalkyl)-3-hydroxypyridin-4-
ones as bidentate iron(III) chelators with potential for oral
administration is described.
The pKa values of the ligands and the stability constants of their
iron
(III) complexes have been determined.
Results indicate that the introduction of a 1‘-hydroxyalkyl group at
the 2-position leads to a significant improvement in the pFe3+
values.
Such an effect was found to be greater with the hydroxyethyl
substituent than with the hydroxymethyl substituent, particularly in
the cases of 1-ethyl-2-(1‘-hydroxyethyl)-3-hydroxypyridin-4-one
(pFe3+
= 21.4) and 1,6-dimethyl-2-(1‘-hydroxyethyl)-3-hydroxypyridin-4-one
(pFe3+ = 21.5) where an enhancement on pFe3+ values in the region of
two orders of magnitude is observed, as compared with Deferiprone
(1,2-
dimethyl-3-hydroxypyridin-4-one) (pFe3+ = 19.4).
The ability of these novel 3-hydroxypyridin-4-ones to facilitate the
iron excretion in bile was investigated using a [59Fe]ferritin-loaded
rat model.
Chelators and prodrug chelators possessing high pFe3+ values show
great promise in their ability to remove iron under in vivo
conditions.
-------------------------
Synthesis, antimicrobial evaluation and QSAR study of some 3-
hydroxypyridine-4-one and 3-hydroxypyran-4-one derivatives
Afshin Fassihia, , , Daryoush Abedib, Lotfollah Saghaiea, Razieh
Sabeta, Hossein Fazelic, Ghasem Bostakia, Omid Deilamia and
Hekmatollah Sadinpoura
aDepartment of Medicinal Chemistry, Faculty of Pharmacy, Isfahan
University of Medical Sciences, Hezar Jerib, 81746-73461 Isfahan,
Islamic Republic of Iran
bDepartment of Biotechnology, Faculty of Pharmacy, Isfahan University
of Medical Sciences, Hezar Jerib, 81746-73461 Isfahan, Islamic
Republic of Iran
cDepartment of Microbiology, Faculty of Medicine, Isfahan University
of Medical Sciences, Hezar Jerib, 81746-73461 Isfahan, Islamic
Republic of Iran
Received 9 July 2008; revised 15 October 2008; accepted 20 October
2008. Available online 30 October 2008.
Abstract
A series of Mannich bases of 2-alkyl-3-hydroxy-pyridine-4-ones,
namely
2-alkyl-3-hydroxy-5-N-piperidylmethyl or N,N-dialkylaminomethyl
pyridine-4-ones 9, 10 and 15–18, two derivatives of N-aryl-2-
methyl-3-
hydroxy-pyridine-4-ones 19, 20 and two N-alkyl derivatives of maltol,
21 and 22 were prepared.
They were screened for their antibacterial and antifungal activities
against a variety of microorganisms using micro plate Alamar Blue®
assay (MABA) method. Multiple linear regressions (MLR) analysis was
performed for the synthesized compounds as well as a series of
pyridinone and pyranone derivatives 23–43 which have been synthesized
and evaluated for antimicrobial activity by other researchers
previously.
Studied compounds showed a better quantitative structure–activity
relationship (QSAR) model for the antimicrobial activity against
Candida albicans and Staphylococcus aureus in comparison with other
tested microorganisms.
doi:10.1016/j.ejmech.2008.10.022
-------------------
"Chelators of synthetic or plant origin may carry less risk"
The effect of synthetic iron chelators on bacterial growth in human
serum
J.H. Brock a , Joan Licéaga a G.J. Kontoghiorghes b
a University Department of Bacteriology and Immunology, Western
Infirmary, Glasgow, USA b Department of Haematology, Royal Free
Hospital, London, U.K.
Correspondence to: Dr. J.H. Brock, Dept. of Bacteriology and
Immunology, Western Ifirmary, Glasgow, G11 6NT, Scotland, U.K.
Copyright 1988 Federation of European Microbiological Societies
KEYWORDS
Iron • Chelator • Bacterial growth • Infection
ABSTRACT
Abstract The effect of synthetic iron chelators of the 1-alkyl-3-
hydroxy-2-methylpyrid-4-one class (the L1 series) and 1-
hydroxypyrid-2-
one (L4) on bacterial growth in human serum was compared with those
of
the plant iron chelators mimosine and maltol and of the microbial
siderophore desferrioxamine.
None of the synthetic chelators enhanced growth of 3 Gram-negative
organisms (Yersinia enterocolitica, Escherichia coli and Pseudomonas
aeruginosa); in some cases they were even inhibitory.
L4 strongly stimulated growth of Staphylococcus epidermidis, but the
L1 series had only a marginal effect.
Maltol was mildly inhibitory to all 4 bacterial species, while
mimosine enhanced the growth of S. epidermidis and Y. enterocolitica
but had little effect on E. coli or P. aeruginosa. Desferrioxamine
enhanced the growth.
Chelators of synthetic or plant origin may carry less risk of
increasing susceptibility to bacterial infection in patients
undergoing chelation therapy for iron overload than does
desferrioxamine, the drug currently in clinical use.
FEMS Microbiology Letters
Volume 47 Issue 1, Pages 55 - 60
Published Online: 27 Mar 2006
© 2008 Federation of European Microbiological Societies. Published by
Blackwell Publishing Ltd. All rights reserved
--------------------------------------------------------------------------------
Received 23 September 1987, Accepted 4 November 1987
DIGITAL OBJECT IDENTIFIER (DOI)
10.1111/j.1574-6968.1988.tb02490.x About DOI