Mycophenolic acid

Structural formula
General
Non-proprietary name	Mycophenolic acid
other names	( E ) -6- (4-Hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydroisobenzofuran-5-yl) -4-methylhex-4-enoic acid ( IUPAC ) ; Acidum mycophenolicum ( Latin ) ;
Molecular formula	C 17 H 20 O 6
Brief description	white to almost white, crystalline powder
External identifiers / databases
EC number	246-119-3
ECHA InfoCard	100,041,912
PubChem	446541
ChemSpider	393865
DrugBank	DB01024
Wikidata	Q420553
Drug information
ATC code	L04 AA06
Drug class	Immunosuppressants
Mechanism of action	selective, non-competitive and reversible inhibitor of IMPDH
properties
Molar mass	320.34 g · mol -1
Physical state	firmly
Melting point	141 ° C (needles from hot water)
pK s value	4.5
solubility	almost insoluble in cold water; easily soluble in ethanol ; sparingly soluble in diethyl ether and chloroform ; sparingly soluble in toluene
safety instructions
	Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed
H and P phrases	H: 302-341
	P: 281
Toxicological data	352 mg kg −1 ( LD 50 , rat , oral )
	As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Mycophenolic acid was the first well-characterized example of an antibiotic . It was isolated and crystallized by Bartolomeo Gosio in 1893 . He observed that it inhibited the growth of anthrax pathogens.

Gosio was actually investigating the vitamin deficiency disease pellagra , the cause of which he suspected to be a fungal infection of corn. He isolated a mold that he believed to be Penicillium glaucum , but which was probably Penicillium brevicompactum . From the filtrates of this organism he crystallized a substance with phenolic properties, which together with iron (III) chloride solutions gave a blue to violet color. He didn't give it a name because he thought it was p -hydroxyhydrocinnamic acid. The substance inhibited the development of anthrax pathogens, as Gosio provisionally announced in 1893. In 1896 he summarized his findings again.

When the search for further antibiotics began after the discovery of penicillin , mycophenolic acid was rediscovered at least twice. However, the co-discoverer of penicillin Howard Florey recognized Gosio's achievement with the words: "mycophenolic acid enjoys the distinction of being the first antibiotic produced by a mold to be crystallized" . The correct structure was only clarified by Birkinshaw in 1952. In addition to bacteria, mycophenolic acid is also effective against fungi, viruses and tumor cells. It has been used clinically to treat psoriasis .

Mycophenolic acid selectively inhibits the enzyme inosine monophosphate dehydrogenase , which is important for the formation of DNA in cells, especially in the lymphocytes . By preventing the production of new DNA, mycophenolic acid reduces the speed of lymphocytes and thus has an immunosuppressive effect . An ester of mycophenolic acid, mycophenolate mofetil , is used to suppress organ rejection after kidney and heart transplants. After administration, free mycophenolic acid is produced again in the body from the ester.

literature

Ronald Bentley: Bartolomeo Gosio, 1863-1944: An Appreciation . In: Advances in Applied Microbiology . Vol. 48, 2001, pp. 229-250.

Individual evidence

↑ ^a ^b ^c ^d data sheet Mycophenolic acid from Sigma-Aldrich , accessed on April 12, 2011 ( PDF ).
^ ^A ^b ^c The Merck Index : An Encyclopedia of Chemicals, Drugs, and Biologicals , 14th Edition (Merck & Co., Inc.), Whitehouse Station, NJ, USA, 2006; ISBN 978-0-911910-00-1 .
↑ Bartolomeo Gosio: Contributo all'etiologia della pellagra; ricerche chimiche e batteriologiche sulle alterazioni del mais. In: Giornale della Reale Accademia di Medicina di Torino . Vol. 61, 1893, pp. 484-487.
↑ Bartolomeo Gosio: Ricerche batteriologiche e chimiche sulle alterazioni del mais. Contributo all'etiologia della pellagra . In: Rivista d'Igiene e Sanità Pubblica . Vol. 7, No. 21, 1896, pp. 484-487 and No. 22, pp. 869-888.
↑ HW Florey, MA Jennings, K. Gilliver, AG Sanders: Mycophenolic Acid. An Antibiotic from Penicillium brevicompactum Dierckx. In: The Lancet . Vol. 247, No. 6385, 1946, pp. 46-49.
↑ JH Birkinshaw, H. Raistrick and DJ Ross: Studies in the biochemistry of micro-organisms. 86. The molecular constitution of mycophenolic acid, a metabolic product of Penicillium brevi-compactum Dierckx. Part 3. Further observations on the structural formula for mycophenolic acid. In: Biochemical Journal . Vol. 50, 1952, pp. 630-634.

[Sigma-1] ta sheet Mycophenolic acid from Sigma-Aldrich , accessed on April 12, 2011 ( PDF ).

[MERCK_Index-2] A ^b ^c The Merck Index : An Encyclopedia of Chemicals, Drugs, and Biologicals , 14th Edition (Merck & Co., Inc.), Whitehouse Station, NJ, USA, 2006; ISBN 978-0-911910-00-1 .

[3] Bartolomeo Gosio: Contributo all'etiologia della pellagra; ricerche chimiche e batteriologiche sulle alterazioni del mais. In: Giornale della Reale Accademia di Medicina di Torino . Vol. 61, 1893, pp. 484-487.

[4] Bartolomeo Gosio: Ricerche batteriologiche e chimiche sulle alterazioni del mais. Contributo all'etiologia della pellagra . In: Rivista d'Igiene e Sanità Pubblica . Vol. 7, No. 21, 1896, pp. 484-487 and No. 22, pp. 869-888.

[5] HW Florey, MA Jennings, K. Gilliver, AG Sanders: Mycophenolic Acid. An Antibiotic from Penicillium brevicompactum Dierckx. In: The Lancet . Vol. 247, No. 6385, 1946, pp. 46-49.

[6] JH Birkinshaw, H. Raistrick and DJ Ross: Studies in the biochemistry of micro-organisms. 86. The molecular constitution of mycophenolic acid, a metabolic product of Penicillium brevi-compactum Dierckx. Part 3. Further observations on the structural formula for mycophenolic acid. In: Biochemical Journal . Vol. 50, 1952, pp. 630-634.