Anti-Infective Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry - Anti-Infective Agents) - Volume 8, Issue 3, 2009

Terpenoids, biosynthetically related ubiquitous compounds found in virtually all living organisms from marine invertebrates to blooming plants, are derived from the same precursor but their structures and biological and/or pharmacological activities are widely different. Our review concerns terpenoid compounds with antiviral activities, from the simplest sesquiterpenes to diterpenes and sesterterpenes. They include commercially produced therapeutics, compounds with documented antiviral effects and potential future medical use, as well as substances in different stages of clinical research and testing. All of them are based on natural compounds, with only partial man-made changes in the basic structure or mere substituent modifications.

Terpenoid compounds of natural origin with antiviral activities, namely triterpenes and steroids, include compounds with potential future medical use as well as substances in different stages of clinical research and testing. These natural compounds have often been synthetically modified, the modification including both changes in the basic structure or mere substituent modifications.

Pasteur and Joubert, in 1877, were among the first to recognize the potential of microbial products as therapeutic agents and demonstrated that common microorganisms could inhibit the growth of Anthrax bacilli. However, the milestone in the field of antimicrobial agents was the advent of penicillin, in 1928, by Alexander Fleming from a strain of the mold Penicillium. Since then, the fungi and higher plants have been searched for the production/preparation of novel antibacterial compounds, including cephalosporins and aminoglycosides. However, due to increasing usage and selection pressure, bacteria have started expressing resistance to these compounds. Hence, there is an urgent need to review and search for newer antibacterial compounds derived from plant species. In this review, the potential of plant species to yield newer antibacterial agents will be illustrated with an emphasis on compounds exclusively isolated in very recent years. Some of the issues pertinent to this area will be briefly reviewed and it is hoped that this would definitely stimulate further discussions and research on this important aspect.

The mounting incidences of drug resistance of the unicellular eukaryotes along with insecticide- resistant vectors are the foremost factors contributing towards the amplified prevalence of tropical diseases in underdeveloped and developing countries. Malaria and leishmaniasis are two most significant parasitic diseases endemic in these regions and result in high rates of mortality and pose an additional socio- economic burden. Being short of effective immunoprophylaxis; relevant preventive sanitary measures and pharmacological approaches are needed to empower the undesirable effects of these diseases. Current antiparasitic chemotherapy is expensive, has undesirable side effects, or is marginally effective due to the problem of resistance. Collaboration of molecular biology and drug discovery approaches are required, which could lead to identification of new drug targets for efficient chemotherapeutic intervention. The recent trend in identification of drugable targets has provided a new leap in the study of the structural determinants which could be effectively targeted. The present review highlights the various chemotherapies available in the area of malaria and leishmaniasis and novel metabolic and enzymatic pathways which are being pursued for new drug discovery endeavors.

The interactions between bovine serum albumin and phenols have been studied by cyclic voltammetry (CV). The interaction divides into specific and non-specific binding sites, and mainly ascribes to the electronic force. One specific binding site between bovine serum albumin and p-aminophenol (p-AP) as well as p-quinonimine (p-AQ) is obtained. Both the specific binding number of p-AP and p-AQ binding bovine serum albumin were in the ratio of 5:1. Two specific binding sites for p-hydroquinone (p-HQ) and p-benzoquinone (p-BQ) were found, respectively. The specific binding number of p-HQ are 15:1 and 9:1, respectively, while total specific binding number was 26:1. Moreover, the specific binding number of p-BQ was 15:1 and 9:1, respectively, with total specific binding number was 26:1. Three specific binding sites for pyrocatechol (PC) were obtained, and two specific binding sites for o-benzoquinone (o-BQ) were observed. The specific binding number of PC are 11:1, 3:1 and 8:1, respectively, total specific binding number being 22:1. However, the specific binding number of o-BQ was 3:1 and 5:1 respectively, with total specific binding number being 8:1.

Infection specific radiopharmaceuticals can be used for diagnosis, decision-making in therapy and treatment follow-up. Research has been ongoing to develop infection specific markers since clinically used tracers cannot discriminate between infection and inflammation. A specific radiopharmaceutical for infection imaging should satisfy the following criteria: high and specific uptake at the infection site, rapid infection detection and background clearance, minimal accumulation in non-target tissues, low toxicity, zero immune response and especially the ability to differentiate infection from sterile inflammation. Radiolabeled anti-infective agents can fulfill the majority of these requirements. Technetium- 99m (99mTc) labeled antibiotics have potential to differentiate sterile inflammation from infection. There are numerous studies reporting the use of radiolabeled antibacterial and antifungal agents for infection detection. Other promising agents are antimicrobial peptides (AMPs) since they preferentially bind to bacteria membranes instead of those of mammalian cells thus distinguishing between infection and sterile inflammation. Synthetic AMPs derived from human natural peptides offers possibility for studying the effects of polymerization and substituting the amino acid sequence to design a specific micro-organism seeking tracer. 99mTc-labeled anti-infectives are ideal as infection-seeking agents because of its direct and fast accumulation. Clinical studies already undertaken and further evaluation with different pathogen types such as viruses, fungi, parasites and intracellular pathogens in humans will improve the potential of these compounds. Radiochemical techniques for labeling anti-infectives have been developed to optimize biodistribution and targeting properties of tracers. An important issue is the technetium-99m specific coordination site in the anti-infective molecule and its chemical and biochemical characterization.