Editorial

Antibiotic discovery and development have undergone major changes in the new millennium, namely changes in the molecular chemotypes that are being examined as new anti-infectives and in regimens of treatment. Chemical structures that were of minor scientific interest years ago, now have more research devoted to them by diligent and determined researchers throughout the world- and this is happening for a number reasons. The first and foremost is that it is getting more and more difficult to keep up with antibiotic resistance mechanisms, as the generations of penicillins, cephalosporins and other common antibiotics increase in number and decrease in activity. The second major reason for renewed interest in other families of molecules is that it is just getting more difficult to chemically modify and deliver active antibiotics, as mechanisms of resistance increase. The goal of this review journal, as I see it as the Editor-in-Chief, is to follow the scientific trends in antibiotic drug discovery, development and chemotherapy, and report back to the reader, illuminating the complexities and findings of the different families of antibiotics, particularly in regards to their structure-versus-activity profiles, in an approving nod to all medicinal chemists. It is also hoped that from this journal and the information it presents other advances in antibiotic evolution occur, from the motivation and insight gained from our authors in the various contemporary and timely topics. And as antibiotics evolve, so will our ability to treat infectious diseases-eventually. The editorial and advisory board members (EABM) of Anti-infective Agents in Medicinal Chemistry are researchers and experts active in diverse fields of chemotherapy devoted to infectious diseases, and with Bentham Publishers, make every effort to deliver the most current and relevant topics and scientific fronts in their fields. The time they spend composing, writing and editing is considerable and admirable, seeking to increase and compile the body of knowledge for future researchers, and to help their field progress and evolve. After all, in a changing biological world you either adapt or die, and this rudimentary adage is applicable to anti-infective agents and the future of chemotherapy. This special issue highlights the research interests of members of our Editorial and Advisory Board, experts in different fields that strive to educate others of the importance of their studies and detail the molecular worlds they can share. Our article on Polyfunctional Antibiotics Affecting Bacterial Cell Membranes, written by myself and my colleagues at Paratek and microbiologist Dr. Susan Barbaro of Rivier College, presents a series of families of compounds of increasing molecular complexity that have one common mechanistic feature- the ability to perturb bacterial membranes and affect antibiosis. This common denominator is also the reason behind the recent success of Cubist Pharmaceuticals and their lipopeptide Cubicin® for use against resistant bacteria and in complicated skin and tissue infections. From the study of these other families will no doubt evolve newer and more potent antibiotics with increased specificity for bacteria and less toxic side effects in mammals. The families presented range from low molecular weight compounds to the broad array of antimicrobial peptides, which by themselves are a separate scientific front and will be the subject of future articles. Continuing in this theme of membrane active agents is the review by Dr. Brandenburg and his colleagues, describing their studies of the antimicrobial and anti-inflammatory peptide melittin and its effects on cellular membranes. Here, their group describes the mechanisms of action of melittin in great detail using the latest methods in analytical chemistry to understand and correlate with biological test systems. Their efforts demonstrate the state-of-the-art in membrane physiology and binding stoichiometry and are novel methods for studying bacterial and mammalian cell membranes while they further the evolution of science. One area of antibiotic evolution that is a divergence from the normal is the finding that certain classes of antibiotics have other mechanisms of action as anti-inflammatory agents in eukaryotic cells and may show therapeutic benefit in mammals. Drs. Konaklieva and Plotkin and their colleague T. Herbert explain their findings and activities of the β-lactam family of antibiotics against eukaryotic cells, particularly those involved in neural tissue. The β-lactams hold promise as neuroprotectants independent of their antibiotic effects, and out of the large number of compounds synthesized in the past they surely will emerge as SAR and clinical candidates.