Recent Patents Reveal Microtubules as Persistent Promising Target for Novel Drug Development for Cancers

Abstract

Conventionally, the successful targets for the drug development in cancer range from the DNA damage, replication, signal transduction pathways, hormones, cytokines, anti-angiogenic agents, and radio/photo-sensitizers. They dominate the therapeutic arena after the initial debulking surgery. More recently, tubulin, the primary constituent of microtubules (MTs), has made a fairly successful debut in the therapeutic armamentarium. Tubulin binding drugs come in two classes: that depolymerize microtubules and that over-polymerize and bundle them. Microtubule (MT) binding drugs are in some ways superior in nature primarily because of their less debilitating side effects when compared to the generalized DNA metabolism targeting agents, and many new promising patents are being funneled into the drug development pipeline. Nevertheless, many of these relatively new agents still face challenges relating to their delivery methods, bioavailability, toxicities, and the inevitable resistance shared by all chemotherapeutics. Finally, we disclose a new genre of anti-MT drugs, noscapinoids that have just begun climbing the clinical trials ladder. The lead compound, noscapine, is a plant derived, orally available, minimally-toxic (if at all) agent that has shown phenomenal promise in the preclinical experimentation and Phase-I clinical trial. A rational approach based upon the precise molecular model of the tubulin-noscapine complex is bound to inspire novel and better therapeutic analogs in future.

Synthesis and Biological Evaluation of N‐Substituted Noscapine Analogues

“…in the 1990s 2. The rational structure‐based screening of naturally derived compounds sharing structural similarities with toxic microtubule‐depolymerising agents such as colchicine and podophyllotoxin demonstrated noscapine to possess both the structural and binding similarities of these previously known microtubule (MT) depolymerising compounds 4. Subsequent biological testing of noscapine showed enhanced qualities over current tubulin binding agents.…”

Synthesis and Pharmacological Evaluation of N-(3-(1H-Indol-4-yl)-5-(2-methoxyisonicotinoyl)phenyl)methanesulfonamide (LP-261), a Potent Antimitotic Agent

“…Microtubules are highly dynamic noncovalent polymers formed by tubulin heterodimers consisting of α- and β-tubulin. They are major components of the cytoskeleton of all eukaryotic cells and play a vital role in maintenance of cell shape and cell signaling . The elongation and shortening of the microtubules are critical to mitosis.…”

Synthesis and Biological Evaluation of Indolyl Bis-chalcones as Anti-Breast Cancer and Antioxidant Agents

“…Most of the cancer treatment is the use of surgery, radiation and chemotherapy. [2] Most of the marketed chemotherapeutic agents suffer from serious and sometimes intolerable toxic effects. So, the development of novel anticancer agents is a crucial need of time.…”