Abstract
Microtubules form crucial dynamic structural cellular components of the cell and are composed of the alpha beta tubulin heterodimers. Microtubules are involved in a wide variety of functions in the cell such as attribution to cell shape, motility, intracellular trafficking and mitotic spindle formation. Owing to these reasons, tubulin and microtubules have gained significant interest as important targets for cancer therapy. A review of the existing microtubule targeting drugs specifies that these agents can be categorised into two of the major categories: Microtubule stabilizing agents such as paclitaxel, docetaxel, epothilones, and discodermolide which bind to the tubulin polymer and stabilize the microtubules, microtubule destabilizing agents such as vinca alkaloids, colchicine and combretastatins which bind to tubulin dimers and cause destabilization. These agents ultimately alter the equilibrium between tubulin and microtubule resulting in disruption of mitotic spindle, thereby effecting a critical transition in the cell cycle, leading to cell death. Further, clinical studies of these agents are limited by toxicity effects and emergence of drug resistance. The hybrid drugs are a combination of two or more drugs wherein pharmacophores are incorporated into a single molecule to interact with multiple targets and enhance the cytotoxic action with minimal side effects. Such hybrid regimens can improve therapeutic efficacy and reduce drug toxicity. Therefore, studies on new hybrids with such biological properties form important part in chemistry. In this review, we present an overview of various recent hybrids of colchicines, combretastatin, phodophyllotoxin, etc generated by combination among themselves through linkers or with other pharmacophores and their properties like tubulin stabilization and tubulin destabilization. We also attempted to provide chemistry, toxicity, resistance, side effects of these molecular hybrids acting as microtubule targeting drugs.
Keywords: Paclitaxel, Docetaxel, Epothilones, Vinca Alkaloids, Colchicine, Cancer Chemotherapeutics.
Graphical Abstract
Call for Papers in Thematic Issues
Chemistry Based on Natural Products for Therapeutic Purposes
The development of new pharmaceuticals for a wide range of medical conditions has long relied on the identification of promising natural products (NPs). There are over sixty percent of cancer, infectious illness, and CNS disease medications that include an NP pharmacophore, according to the Food and Drug Administration. Since NP ...read more
Current Trends in Drug Discovery Based on Artificial Intelligence and Computer-Aided Drug Design
Drug development discovery has faced several challenges over the years. In fact, the evolution of classical approaches to modern methods using computational methods, or Computer-Aided Drug Design (CADD), has shown promising and essential results in any drug discovery campaign. Among these methods, molecular docking is one of the most notable ...read more
Drug Discovery in the Age of Artificial Intelligence
In the age of artificial intelligence (AI), we have witnessed a significant boom in AI techniques for drug discovery. AI techniques are increasingly integrated and accelerating the drug discovery process. These developments have not only attracted the attention of academia and industry but also raised important questions regarding the selection ...read more
From Biodiversity to Chemical Diversity: Focus of Flavonoids
Flavonoids are the largest group of polyphenols, plant secondary metabolites arising from the essential aromatic amino acid phenylalanine (or more rarely from tyrosine) via the phenylpropanoid pathway. The flavan nucleus is the basic 15-carbon skeleton of flavonoids (C6-C3-C6), which consists of two phenyl rings (A and B) and a heterocyclic ...read more
Related Journals
Anti-Cancer Agents in Medicinal Chemistry
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry
Current Bioactive Compounds
Current Cancer Drug Targets
Combinatorial Chemistry & High Throughput Screening
Current Cancer Therapy Reviews
Current Diabetes Reviews
Current Drug Safety
Current Drug Targets
Current Drug Therapy
Related Books
Drug Addiction Mechanisms in the Brain
The NLRP3 Inflammasome: An Attentive Arbiter of Inflammatory Response
Botanicals and Natural Bioactives: Prevention and Treatment of Diseases
Software and Programming Tools in Pharmaceutical Research
Objective Pharmaceutics: A Comprehensive Compilation of Questions and Answers for Pharmaceutics Exam Prep
Medicinal Chemistry of Drugs Affecting Cardiovascular and Endocrine Systems
Frontiers In Medicinal Chemistry
Advanced Pharmacy
Plant-derived Hepatoprotective Drugs
Frontiers in Natural Product Chemistry
100
11
