Antimitotic

A new antitumor drug, taxol, has been isolated from the bark of Taxus brevifolia, the Pacific yew tree. Like vinblastine and colchicine, taxol inhibits cell replication by acting on microtubules. Unlike these other antimitotic drugs, however, taxol stimulates microtubule polymerization and stabilizes microtubules. 

The remarkable success of taxol in treatment of breast and ovarian cancers stimulated research efforts to synthesize taxol directly and to identify new antimitotic agents that, like taxol, stimulate microtubule polymerization. 

Synthetic study of 4-thiazoline derivative curacin A, a novel antimitotic agent isolated from cyanobacterium Lyngbya majuscula 99YGK552. 

The active principle of the autumn crocus (Colchicum autumnale), colchicine (48), is one of the very few drugs that have remained in reputable medical use since ancient times. This drug was the only useful treatment available for the excruciating pain associated with crystallization of uric acid in the joints characteristic of gout until the advent of allopurinol. Although the precise mechanism by which colchicine gives this dramatic relief remains undefined, the antimitotic activity of this agent is... 

In addition, the alkaloid colchicine (from Colchicum autumnale) blocks tubulin polymerization by binding to heterodimeric (3-tubulin between amino acids 239 and 254. Since it inhibits the MT-dependent migration of granulocytes into areas of inflammation and their MT-dependent release of proinflammatory agents, it is used to treat attacks of gout. Its antimitotic effect in the gastrointestinal system induces diarrhoea. Nocodazole competes for the binding site of colchicine and has similar effects on heterodimeric (3-tubulin. 

Mitotic inhibitors (antimitotics) interfere with or stop cell division. Examples of mitotic inhibitors include paclitaxel (Taxol) and vincristine (Oncovin). 

The fungal metabolite (+)-brefeldin A (325) displays potent antitumor, antifungal, antiviral, antimitotic, and immunosuppressive activities. Recently, Romo and Wang described a highly concise total synthesis of 325 by a combined /J-lactone-CM approach (Scheme 63), that again underlines the high tolerance of sensitive functionality exhibited by the second-generation Ru catalysts [ 145]. 

Podophyllotoxin, a plant lignan, is a potent antimitotic agent (Figure 6.61). An enantioselective synthesis of (—)-podophyllotoxin was achieved via the enzymatic desymmetrization of an advanced meso-diacetate, through PPL-mediated diester hydrolysis [157]. 

Noitrachelogenin, Wikstroemia indica SiOi CHCI3 + MeOH FeCl3 and UV Antifungal, antimitotic, 88... 

Polyalkylcyanoacrylate 0.2 Lysosomtropic after intravenous injection Antimitotics (e.g., daunorubicin, actinomycin D, doxorubicin)... 

Shi Q, Chen K, Li L, et al. Antitumor agents, 154. Cytotoxic and antimitotic flavonols from Polanisia dodecandra. J Nat Prod 1995 58 475-482. 

The relative and absolute stereochemistry of antimitotic macrolide archazolid A and B, originally isolated in the early nineties, has been determined on the basis of extensive high-field NMR studies, molecular modelling and chemical derivatization <06OL4751>. The proposed structures have yet to be confirmed by total synthesis. 

Colchicine is an antimitotic drug that is highly effective in relieving acute gout attacks but has a low benefit-toxicity ratio. When colchicine is started within the first 24 hours of an acute attack, about two-thirds of patients respond within several hours. The likelihood of success decreases substantially if treatment is delayed longer than 48 hours after symptom onset. 

Many attempts to alter the physical properties of neomycin by the formation of various salts have been described. Thus the neomycin salts of the higher fatty acids, such as the stearate, palmitate and myristate3(3 31 were prepared and being water-insoluble were formulated in ointment bases. Similarly, the undecylenate salt has been prepared and processes for its production patented3 33 34 The undecylenate and caprylate salts have been described as being particularly suitable as antimitotic compounds35. 

The compound curacin A 207 is a novel antimitotic agent isolated from the Caribbean cyanobacterium Lyngbya majuscula. The compound consists of a disubstituted thiazoline bearing a chiral cyclopropane ring and an aliphatic side chain. Scheme 5-67 depicts the construction of the cyclopropane ring using an asymmetric cyclopropanation reaction.122... 

Finally, the report by Angenot et al. of an exceptional increase of antimitotic activity in strychnopentamine (104) caused by the presence of a supplementary pyrrolidine ring, is worth noting (199). Chemists might use this fact as an reason to promote interesting new syntheses of pyrrolidine alkaloids or creation of unnatural molecules containing pyrrolidine. 

Colchicine Antimitotic gout anti-inflammatory Inhibits migration of granulocytes leukopenia agranulocytosis... 

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