The ability to affect eukaryotic and prokaryotic cellular growth, signaling and differentiation is a continuing focus in the pharmaceutical industry. The fundamental ability to affect these cellular processes is inherent in lactones. Lactones, which are ubiquitous in nature, reflect a broad phylogenetic diversity indicative of their ability to act as simple alkylating compounds, with their in situ activities falling into one of two categories, i.e., protect or conquer. Medically, their utility as pharmaceutical agents range from that of antimicrobial to anti-neoplastic agent depending on the functional groups attached.

The common practice in antibacterial drug development has been to rapidly make an attempt to find ever-more stable and broad-spectrum variants for a particular antibiotic, once a drug resistance for that antibiotic is detected. We are now facing bacterial resistance toward our clinically relevant antibiotics of such a magnitude that the conversation for antimicrobial drug development ought to include effective new antibiotics with alternative mechanisms of action. The electrophilic β-lactam ring is amenable for the inhibition of different enzyme classes by a suitable decoration of the core scaffold. Monocyclic β-lactams lacking an ionizable group at the lactam nitrogen exhibit target preferences toward bacterial enzymes important for resistance and virulence. The present review intends to draw attention to the versatility of the β-lactams as antimicrobials with “unusual” molecular targets.

Abstract: The number of organosulfur compounds being patented has been growing. A wide variety of these organosulfur compounds, whether naturally occurring or synthetic, exhibit antibacterial properties. Mechanistically, organosulfur groups can act as metal chelators, powerful nucleophiles or electrophiles depending on the local environment in which a given reaction occurs. In this review of the patent literature from 1999-2005, the reliance of these compounds on the reaction of the sulfur moiety with its biological target(s) will be discussed with regards to activity, specificity, and antimicrobial spectrum.

There are two types of bacterial communication systems, those in which the signal produced by bacteria isdirected only at other organisms, and those where the signal is detected by others and self. The latter is involved inadaptation to the environment. The adaptation signals are autoinducers, the response is population density-dependent andhas been termed "quorum sensing". Our current knowledge of bacterial signaling systems indicates that Gram positivebacteria use small peptides for both types of signaling, whereas Gram negative organisms use homoserine lactones asautoinducers. Gram- negative bacteria internalize the signals which act upon an intracellular receptor. Gram-positivebacteria use the signals as ligands for an extracellular receptor of a two-component signaling system. Inhibitors of quorumsensing compounds for both Gram positive and Gram negative bacteria are being explored. Signal inhibitors could bepotentially effective in impeding biofilm formation, which might prolong the utility of the currently available antibioticsin this era of antibiotic resistance. In this review, we will explore both bacteria-host and bacteria-bacteria communicationsystems, with an emphasis on inhibitors of these systems both natural and synthetic.

Fragment-based lead discovery (FBLD) is a powerful application for developing ligands as modulators of disease targets. This approach strategy involves identification of interactions between low-molecular weight compounds (100–300 Da) and their putative targets, often with low affinity (K_D ~0.1–1 mM) interactions. The focus of this screening methodology is to optimize and streamline identification of fragments with higher ligand efficiency (LE) than typical high-throughput screening. The focus of this review is on the last half decade of fragment-based drug discovery strategies that have been used for antimicrobial drug discovery.