A23187

A23187
Identifiers
	IUPAC name 5-(methylamino)-2-({(2R,3R,6S,8S,9R,11R)-3,9,11-trimethyl-8-[(1S)-1-methyl-2-oxo-2-(1H-pyrrol-2-yl)ethyl]-1,7-dioxaspiro[5.5]undec-2-yl}methyl)-1,3-benzoxazole-4-carboxylic acid;
CAS Number	52665-69-7 ;
PubChem CID	11957499;
ChemSpider	10131749 ;
ChEMBL	ChEMBL1256686 ;
CompTox Dashboard (EPA)	DTXSID1040405 ;
ECHA InfoCard	100.052.786
Chemical and physical data
Formula	C29H37N3O6
Molar mass	523.62 g/mol g·mol−1
3D model (JSmol)	Interactive image;
	SMILES O=C(O)c1c(NC)ccc2oc(nc12)C[C@H]5O[C@]3(O[C@@H]([C@H](C)C[C@H]3C)[C@@H](C(=O)c4cccn4)C)CC[C@H]5C;
	InChI InChI=1S/C29H37N3O6/c1-15-10-11-29(17(3)13-16(2)27(38-29)18(4)26(33)20-7-6-12-31-20)37-22(15)14-23-32-25-21(36-23)9-8-19(30-5)24(25)28(34)35/h6-9,12,15-18,22,27,30-31H,10-11,13-14H2,1-5H3,(H,34,35)/t15-,16-,17-,18-,22-,27+,29+/m1/s1 ; Key:HIYAVKIYRIFSCZ-CYEMHPAKSA-N ;
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A23187 is a mobile ion-carrier that forms stable complexes with divalent cations (ions with a charge of +2). A23187 is also known as Calcimycin, Calcium Ionophore, Antibiotic A23187 and Calcium Ionophore A23187. It is produced at fermentation of Streptomyces chartreusensis.

Actions and uses

A23187 has antibiotic properties against gram positive bacteria and fungi. It also acts as a divalent cation ionophore, allowing these ions to cross cell membranes, which are usually impermeable to them.^[1] A23187 is most selective for Mn²⁺, somewhat less selective for Ca²⁺ and Mg²⁺, much less selective for Sr²⁺, and even less selective for Ba²⁺.^[2] The ionophore is used in laboratories to increase intracellular Ca²⁺ levels in intact cells. It also uncouples oxidative phosphorylation, the process cells use to synthesize Adenosine triphosphate which they use for energy. In addition, A23187 inhibits mitochondrial ATPase activity. A23187 also induces apoptosis in some cells (e.g. mouse lymphoma cell line, or S49, and Jurkat cells) and prevents it in others (e.g. cells dependent on interleukin 3 that have had the factor withdrawn).^[3]

Inex Pharmaceuticals Corporation (Canada) reported an innovative application of A23187. Inex used A23187 as a molecular tool in order to make artificial liposomes loaded with anti-cancer drugs such as Topotecan.^[4]

In IVF field, Ca Ionophore can be used in case of low fertilization rate after ICSI procedure, particularly with Globozoospermia (Round Head sperm syndrome), Ca Ionophore will replace absence of sperm acrosom, and plays role in oocyte activation after ICSI. Recommended use is 0.5 microgram/ml twice for 10 min interrupted with fresh media with 30 min incubation, followed with regular injected eggs culture for IVF.^[5]

Biosynthesis

The core biosynthetic enzymes are thought to include 3 proteins for the biosynthesis of the α-ketopyrrole moiety, 5 for modular type I polyketide synthases for the spiroketal ring, 4 for the biosynthesis of 3-hydroxyanthranilic acid, an N-methyltransferase tailoring enzyme, and a type II thioesterase.^[6]

Commercial availability

Commercially, A23187 is available as free acid, Ca²⁺ salt, and 4-brominated analog.^[7]

References

^ "A23187". Medical Dictionary Online. 2006. Archived from the original on 10 December 2006. Retrieved 2006-11-01. {{cite web}}: Unknown parameter |deadurl= ignored (|url-status= suggested) (help)
^ Abbott, Bernard; D S Fukuda; D E Dorman; J L Occolowitz; M Debono; L Farhner (1979). "Microbial transformation of A23187, a divalent cation ionophore antibiotic". Antimicrobial Agents and Chemotherapy. 16 (6): 808–812. doi:10.1128/aac.16.6.808. PMC 352958. PMID 119484.
^ "A23187". Archived from the original on 3 November 2006. Retrieved 2006-11-01. {{cite web}}: Unknown parameter |deadurl= ignored (|url-status= suggested) (help)
^ Liposomal Encapsulation of Topotecan Enhances Anticancer Efficacy in Murine and Human Xenograft Models Cancer Research
^ Effect of calcium ionophore on unfertilized oocytes after ICSI cycles; Iran J Reprod Med Vol. 10. No. 2. pp: 83-86, March 2012.
^ Wu Q, Liang J, Lin S, Zhou X, Bai L, Deng Z, Wang Z (March 2011). "Characterization of the biosynthesis gene cluster for the pyrrole polyether antibiotic calcimycin (A23187) in Streptomyces chartreusis NRRL 3882". Antimicrob Agents Chemother. 55 (3): 974–82. doi:10.1128/AAC.01130-10. PMC 3067094. PMID 21173184.{{cite journal}}: CS1 maint: multiple names: authors list (link)
^ A23187 product page from Fermentek

External links

A23187 from AG Scientific, another vendor
A21387 from BIOMOL, a vendor's product page
Calcimycin from Bioaustralis, a vendor's product page

[1] "A23187". Medical Dictionary Online. 2006. Archived from the original on 10 December 2006. Retrieved 2006-11-01. {{cite web}}: Unknown parameter |deadurl= ignored (|url-status= suggested) (help)

[2] Abbott, Bernard; D S Fukuda; D E Dorman; J L Occolowitz; M Debono; L Farhner (1979). "Microbial transformation of A23187, a divalent cation ionophore antibiotic". Antimicrobial Agents and Chemotherapy. 16 (6): 808–812. doi:10.1128/aac.16.6.808. PMC 352958. PMID 119484.

[A23-3] "A23187". Archived from the original on 3 November 2006. Retrieved 2006-11-01. {{cite web}}: Unknown parameter |deadurl= ignored (|url-status= suggested) (help)

[4] Liposomal Encapsulation of Topotecan Enhances Anticancer Efficacy in Murine and Human Xenograft Models Cancer Research

[5] Effect of calcium ionophore on unfertilized oocytes after ICSI cycles; Iran J Reprod Med Vol. 10. No. 2. pp: 83-86, March 2012.

[6] Wu Q, Liang J, Lin S, Zhou X, Bai L, Deng Z, Wang Z (March 2011). "Characterization of the biosynthesis gene cluster for the pyrrole polyether antibiotic calcimycin (A23187) in Streptomyces chartreusis NRRL 3882". Antimicrob Agents Chemother. 55 (3): 974–82. doi:10.1128/AAC.01130-10. PMC 3067094. PMID 21173184.{{cite journal}}: CS1 maint: multiple names: authors list (link)

[7] A23187 product page from Fermentek

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