Multifunctional compounds: Smart molecules for multifactorial diseases

Multifunctional compounds (MFCs) are designed broadly as hybrid or conjugated drugs or as chimeric drugs from two or more pharmacophores/drugs having specific pharmacological activities. These are capable of eliciting multiple pharmacological actions and have emerged as magic bullets in treatment of multifactorial diseases. Many research articles disclosing the development of such compounds for treatment of multifactorial diseases are published during last 7 years. Some successful MFC candidates for multifactorial CNS disorders include ziprasidone, duloxetine, ladostigil and M-30 whereas sunitinib, lapatinib and synthetic oleandane triterpinoids are the successful MFC candidates for various cancers. Many more compounds derived from berberine, tacrine, artemisnin, quinine, NSAIDs, pralidoxine, donepezil, rivastigmine, curcumin and various antioxidants are under investigations for exploration of their multifunctional potential. In general, MFCs possess the advantages of reduced molecularity, no drug-drug interactions and improved pharmacokinetics and pharmacodynamics. A MFC derived from two or more different pharmacophores exerts its activities by interacting with respective receptors of its constituent pharmacophores. It may also exhibit additional binding interactions with the receptor sites that may be responsible for significantly improved or additional activities. The present review discusses various MFCs developed for specific class of disorders with an aim to provide an insight into the strategies in medicinal chemistry for development of such compounds. (C) 2014 Published by Elsevier Masson SAS.