Covering: up to the end of 2016 Novel antimicrobial drugs are continuously needed to counteract bacterial resistance development. An innovative molecular design strategy for novel antibiotic drugs is based on the hybridization of an antibiotic with a second functional entity. Such conjugates can be grouped into two major categories. In the first category (antimicrobial hybrids), both functional elements of the hybrid exert antimicrobial activity. Due to the dual targeting, resistance development can be significantly impaired, the pharmacokinetic properties can be superior compared to combination therapies with the single antibiotics, and the antibacterial potency is often enhanced in a synergistic manner. In the second category (antimicrobial conjugates), one functional moiety controls the accumulation of the other part of the conjugate, e.g. by mediating an active transport into the bacterial cell or blocking the efflux. This approach is mostly applied to translocate compounds across the cell envelope of Gram-negative bacteria through membrane-embedded transporters (e.g. siderophore transporters) that provide nutrition and signalling compounds to the cell. Such ‘Trojan Horse’ approaches can expand the antibacterial activity of compounds against Gram-negative pathogens, or offer new options for natural products that could not be developed as standalone antibiotics, e.g. due to their toxicity.
21 December 2011 in Chemistry – A European Journal
The isoprenoid stress-associated phytohormone abscisic acid (ABA) has recently been recognized to possess multifaceted biological functions in mammals and to exert potent curative effects in a number of clinically relevant human diseases. Studies with human specimens have unequivocally shown that ABA retains its stress-related functional attributes, previously identified in plants, which contribute to enhanced inflammatory defense mechanisms in mammals. Besides, studies performed in animal models revealed prominent anti-inflammatory properties of ABA as indicated by a marked reduction of immune cell infiltrates at the sites of inflammation. Thus, ABA treatment ultimately leads to the profound improvement of both non-communicable and communicable diseases which are associated with an overall alleviated course of inflammation. In addition to its action on the mammalian immune system, ABA was also shown to exert diverse physiological functions on non-immune components. One of the most remarkable features of ABA is to stimulate and expand mesenchymal stem cells, which may open a new avenue for its potential use in the field of regenerative medicine. Furthermore, ABA has been reported to play an important role in the maintenance of glycemic control. In this review, we summarize current understanding of the significance of ABA in the mammalian system, its prophylactic and therapeutic effects in various disease settings and the future directions for development of ABA as novel drug candidate for the improved treatment of inflammatory and infectious human diseases.