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The drug, a macrolide (polyhydroxylated lactone), is a member of a structural diverse class of compounds called polyketides with notable chemical mechanism of action. It stabilizes the microtubules of target cells, essentially arresting them at a specific stage in the cell cycle and halting cell division.
Colchicine has a narrow therapeutic index, so overdosing is a significant risk. Common side effects of colchicine include gastrointestinal upset, particularly at high doses. [14] Severe side effects may include pancytopenia (low blood cell counts) and rhabdomyolysis (damage to skeletal muscle), and the medication can be deadly in overdose. [11]
Cytoskeletal drugs are small molecules that interact with actin or tubulin.These drugs can act on the cytoskeletal components within a cell in three main ways. Some cytoskeletal drugs stabilize a component of the cytoskeleton, such as taxol, which stabilizes microtubules, or Phalloidin, which stabilizes actin filaments.
Microtubule and tubulin metrics [1]. Microtubules are polymers of tubulin that form part of the cytoskeleton and provide structure and shape to eukaryotic cells. Microtubules can be as long as 50 micrometres, as wide as 23 to 27 nm [2] and have an inner diameter between 11 and 15 nm. [3]
It is closely related to the natural alkaloid colchicine with the replacement of the acetyl group on the amino moiety with methyl, but it is less toxic. It depolymerises microtubules and limits microtubule formation (inactivates spindle fibre formation), thus arresting cells in metaphase and allowing cell harvest and karyotyping to be performed.
It binds colchicine much more slowly than other isotypes of β-tubulin. [29] β1-tubulin, sometimes called class VI β-tubulin, [30] is the most divergent at the amino acid sequence level. [31] It is expressed exclusively in megakaryocytes and platelets in humans and appears to play an important role in the formation of platelets. [31]
Cells treated with cytochalasin B and control group cells could not be distinguished. This indicated, that CB has no significant effect at this stage. CB contains a beta-unsaturated ester which can undergo a Michael-type conjugation with nucleophiles. [22] If this is the case, DNA-adduction might be a plausible reaction afterwards.
In cell biology, microtubule nucleation is the event that initiates de novo formation of microtubules (MTs). These filaments of the cytoskeleton typically form through polymerization of α- and β-tubulin dimers, the basic building blocks of the microtubule, which initially interact to nucleate a seed from which the filament elongates.