Divergent approach to building a latrunculin family derived hybrid macrocyclic toolbox

Microtubules are dynamic structures that undergo cycles of catastrophe and rescue. The microtubules play a central role in cell division by forming the spindle apparatus for segregating the chromosomes. This makes them ideal targets for regulating dividing cells in tumors and malignant cancer cells. Microtubule stabilizing drugs help stabilize the microtubule formation and promote its polymerization. Paclitaxel was the first microtubule stabilizing agent used as anticancer drug in chemotherapy...

Contractile rings are composed of microfilaments and are responsible for separating the daughter cells during cytokinesis. Contractile ring assembly proceeds along with other cell cycle events; however, very few mechanistic details are known about the timing and coordination of the contractile rings with the cell cycle.
A small GTPase, RhoA, controls the function and assembly of the contractile ring. RhoA belongs to the Ras superfamily of proteins. The activation of formins by RhoA promotes...

Cytoskeletal filaments are polymeric forms of smaller protein subunits. However, individual cytoskeletal filaments may easily disassemble or associate with other similar filaments to form rigid structures. Microfilaments, made of actin monomers, rely on actin-binding proteins to form bundles and create networks of individual actin filaments. Microtubules rely on microtubule-associated proteins (MAPs) to form sturdy cylindrical structures. However, the proteins involved in forming complex...

Biological macromolecules are organic compounds, predominantly composed of carbon atoms. The carbon atoms are covalently bonded with hydrogen, oxygen, nitrogen, and other minor elements. There are four major biological macromolecule classes: carbohydrates, lipids, proteins, and nucleic acids.
Most macromolecules are composed of single subunits, or building blocks, called monomers. The monomers combine with each other using covalent bonds to form larger molecules known as polymers.
Conversion of...

Microtubules are hollow cylindrical filaments having a diameter of approximately 25 nm and a length that varies from 200 nm to 25 μm. GTP-bound tubulin subunits form αβ-heterodimers for microtubule assembly. These core building blocks interact longitudinally, polymerizing into protofilaments. The protofilaments then interact with one another through lateral bonding forces to form stable cylindrical microtubules. These cylindrical filaments are dynamic as they undergo repeated...

Microtubules are dynamic structures and can be regulated by microtubule targeting agents (MTAs). Microtubule destabilizing drugs are a class of MTAs that destabilize and prevent microtubules' polymerization. Both natural and synthetic chemicals can be found under this class of drugs. Vincristine and vinblastine, two vinca alkaloids, and colchicine were among the first to be discovered. These drugs can affect cells in various ways, either by inducing a change in cell morphology, preventing...