Combretastatins: An Overview of Structure, Probable Mechanisms of Action and Potential Applications

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ŞEKER KARATOPRAK G., AKKOL E., GENÇ Y., BARDAKCI H., YÜCEL Ç., Sobarzo-Sanchez E.

MOLECULES, cilt.25, sa.11, 2020 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Derleme
  • Cilt numarası: 25 Sayı: 11
  • Basım Tarihi: 2020
  • Doi Numarası: 10.3390/molecules25112560
  • Dergi Adı: MOLECULES
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Aerospace Database, Agricultural & Environmental Science Database, Biotechnology Research Abstracts, CAB Abstracts, Chemical Abstracts Core, Communication Abstracts, EMBASE, MEDLINE, Metadex, Veterinary Science Database, Directory of Open Access Journals, Civil Engineering Abstracts
  • Anahtar Kelimeler: combretaceae, combretastatins, drug discovery, natural compound, nanoformulation, structure-activity relationships, tubulin inhibitors, VASCULAR-TARGETING AGENT, DRUG-DELIVERY SYSTEM, NF-KAPPA-B, ANTINEOPLASTIC AGENTS, BIOLOGICAL EVALUATION, A4 PHOSPHATE, NATURAL-PRODUCTS, A-4 PHOSPHATE, CELL-GROWTH, IN-VITRO
  • Gazi Üniversitesi Adresli: Evet

Özet

Combretastatins are a class of closely related stilbenes (combretastatins A), dihydrostilbenes (combretastatins B), phenanthrenes (combretastatins C) and macrocyclic lactones (combretastatins D) found in the bark of Combretum caffrum (Eckl. & Zeyh.) Kuntze, commonly known as the South African bush willow. Some of the compounds in this series have been shown to be among the most potent antitubulin agents known. Due to their structural simplicity many analogs have also been synthesized. Combretastatin A4 phosphate is the most frequently tested compounds in preclinical and clinical trials. It is a water-soluble prodrug that the body can rapidly metabolize to combretastatin A4, which exhibits anti-tumor properties. In addition, in vitro and in vivo studies on combretastatins have determined that these compounds also have antioxidant, anti-inflammatory and antimicrobial effects. Nano-based formulations of natural or synthetic active agents such as combretastatin A4 phosphate exhibit several clear advantages, including improved low water solubility, prolonged circulation, drug targeting properties, enhanced efficiency, as well as fewer side effects. In this review, a synopsis of the recent literature exploring the combretastatins, their potential effects and nanoformulations as lead compounds in clinical applications is provided.