Cytochalasins

Title: Cytochalasins
Literature References: A class of mold metabolites exhibiting a number of unusual and varied effects on animal cells. More than twenty cytochalasins are known, isolated from several different mold spp. All are characterized by a highly substituted hydrogenated isoindole ring of known configuration to which is fused a macrocyclic ring. This ring may vary from 11 to 14 atoms in size and may be either a carbocycle or a lactone. Isoln and structure of cytochalasins A, B, C, D: Aldridge et al., J. Chem. Soc. C 1967, 1667; eidem, Chem. Commun. 1967, 26; of E and F: Aldridge et al., ibid. 1972, 148. Revised structures of cytochalasins E and F: Aldridge et al., ibid. 1973, 551; Büchi et al., J. Am. Chem. Soc. 95, 5423 (1973). Isoln of H, also known as paspaline-P or kodocytochalasin-1: G. S. Pendse, Experientia 30, 107 (1974). Structure of H: S. A Patwardhan et al., Phytochemistry 13, 1985 (1974); M. A. Beno et al., J. Am. Chem. Soc. 99, 4123 (1977); x-ray crystal and molecular structure: J. A. McMillan et al., Chem. Commun. 1977, 105. Isoln of K, L, M from Chalara microspora and proposed structures: T. Fex, Tetrahedron Lett. 22, 2703 (1981). Isoln of E and K from Aspergillus clavatus and proposed alternate structure of K: P. S. Steyn et al., J. Chem. Soc. Perkin Trans. 1 1982, 541. Partial synthesis of A and B: S. Masamune et al., J. Am. Chem. Soc. 99, 6756 (1977). Total synthesis of B: G. Stork et al., ibid. 100, 7775 (1978). Major biological effects are the blockage of cytoplasmic cleavage by blocking formation of contractile microfilament structures, resulting in multinucleate cell formation, the reversible inhibition of cell movement, and the induction of nuclear extrusion: Carter, Nature 213, 261 (1967); Krishan, J. Cell Biol. 54, 657 (1972); E. D. Korn, Physiol. Rev. 62, 703 (1982). Correlation between effects of cytochalasins on cellular structures and cellular events and those on actin in vitro: I. Yahara et al., J. Cell Biol. 92, 69 (1982). Other reported effects include the inhibition of glucose transport, of thyroid secretion, of growth hormone release, of phagocytosis, and of platelet aggregation and clot contraction. See D. A. Hume et al., Nature 272, 359 (1978). Nomenclature: M. Binder et al., J. Chem. Soc. Perkin Trans. 1 1973, 1146. Reviews: M. Binder, C. Tamm, Angew. Chem. Int. Ed. 12, 370 (1973); R. B. Herbert in The Alkaloids vol. 7, J. E. Saxton, Ed. (The Chemical Society, London, 1977) pp 29-30; W. G. Thilly et al., Front. Biol. 46, 53-64 (1978); L. V. Domnina et al., Proc. Natl. Acad. Sci. USA 79, 7754-7757 (1982); W. Siess et al., ibid. 7709-7713.
Derivative Type: Cytochalasin B
CAS Registry Number: 14930-96-2
CAS Name: (7S,13E,16R,20R,21E)-7,20-Dihydroxy-16-methyl-10-phenyl-24-oxo[14]cytochalasa-6(12),13,21-triene-1,23-dione
Additional Names: (E,E)-16-benzyl-6,7,8,9,10,12a,13,14,15,15a,16,17-dodecahydro-5,13-dihydroxy-9,15-dimethyl-14-methylene-2H-oxacyclotetradec[2,3-d]isoindole-2,18(5H)-dione; phomin
Molecular Formula: C29H37NO5
Molecular Weight: 479.61
Percent Composition: C 72.62%, H 7.78%, N 2.92%, O 16.68%
Literature References: The most important and biologically studied of the cytochalasins. Formerly isolated from cultures of a Phoma sp. and called phomin: Rothweiler, Tamm, Experientia 22, 750 (1966). Physicochemical data: A. E. Pohland et al., Pure Appl. Chem. 54, 2219 (1982).
Properties: Felted needles from acetone, mp 218-221°. Completely stable under normal conditions. Solutions in DMSO show no decrease in potency when stored at 4° for three years (Aldrich data sheet). Solubility (mg/ml at 24°): acetone 10.3; ethanol 35.4; DMSO 371; DMF 492. Insol in water.
Melting point: mp 218-221°
Use: As tools in cytological research and in characterization of polymerization properties of actin, q.v.
Cytochrome c Cytochromes P450 Cytohemin Cytolipin H D-2-Deoxyribose

Cytochalasins are fungal metabolites that have the ability to bind to actin filaments and block polymerization and the elongation of actin. As a result of the inhibition of actin polymerization, cytochalasins can change cellular morphology, inhibit cellular processes such as cell division, and even cause cells to undergo apoptosis.[1] Cytochalasins have the ability to permeate cell membranes, prevent cellular translocation and cause cells to enucleate.[2] Cytochalasins can also have an effect on other aspects of biological processes unrelated to actin polymerization. For example, cytochalasin A and cytochalasin B can also inhibit the transport of monosaccharides across the cell membrane,[2] cytochalasin H has been found to regulate plant growth,[3] cytochalasin D inhibits protein synthesis[4] and cytochalasin E prevents angiogenesis.[5]