Future Medicinal Chemistry 

About: Future Medicinal Chemistry is an academic journal published by Future Science Ltd. The journal publishes majorly in the area(s): Medicine & Chemistry. It has an ISSN identifier of 1756-8919. Over the lifetime, 2372 publications have been published receiving 52768 citations. The journal is also known as: Future Med. Chem..

Biofilm formation mechanisms and targets for developing antibiofilm agents

Abstract: Biofilms are communities of microorganisms that are attached to a surface and play a significant role in the persistence of bacterial infections. Bacteria within a biofilm are several orders of magnitude more resistant to antibiotics, compared with planktonic bacteria. Thus far, no drugs are in clinical use that specifically target bacterial biofilms. This is probably because until recently the molecular details of biofilm formation were poorly understood. Bacteria integrate information from the environment, such as quorum-sensing autoinducers and nutrients, into appropriate biofilm-related gene expression, and the identity of the key players, such as cyclic dinucleotide second messengers and regulatory RNAs are beginning to be uncovered. Herein, we highlight the current understanding of the processes that lead to biofilm formation in many bacteria.

Cannabinoids as novel anti-inflammatory drugs

Abstract: Cannabinoids are a group of compounds that mediate their effects through cannabinoid receptors. The discovery of Δ9-tetrahydrocannabinol (THC) as the major psychoactive principle in marijuana, as well as the identification of cannabinoid receptors and their endogenous ligands, has led to a significant growth in research aimed at understanding the physiological functions of cannabinoids. Cannabinoid receptors include CB1, which is predominantly expressed in the brain, and CB2, which is primarily found on the cells of the immune system. The fact that both CB1 and CB2 receptors have been found on immune cells suggests that cannabinoids play an important role in the regulation of the immune system. Recent studies demonstrated that administration of THC into mice triggered marked apoptosis in T cells and dendritic cells, resulting in immunosuppression. In addition, several studies showed that cannabinoids downregulate cytokine and chemokine production and, in some models, upregulate T-regulatory cells (Tregs) as a mechanism to suppress inflammatory responses. The endocannabinoid system is also involved in immunoregulation. For example, administration of endocannabinoids or use of inhibitors of enzymes that break down the endocannabinoids, led to immunosuppression and recovery from immune-mediated injury to organs such as the liver. Manipulation of endocannabinoids and/or use of exogenous cannabinoids in vivo can constitute a potent treatment modality against inflammatory disorders. This review will focus on the potential use of cannabinoids as a new class of anti-inflammatory agents against a number of inflammatory and autoimmune diseases that are primarily triggered by activated T cells or other cellular immune components.

Inhibition of Ras for cancer treatment: the search continues

Abstract: The RAS oncogenes (HRAS, NRAS and KRAS) comprise the most frequently mutated class of oncogenes in human cancers (33%), thus stimulating intensive effort in developing anti-Ras inhibitors for cancer treatment. Despite intensive effort, to date, no effective anti-Ras strategies have successfully made it to the clinic. We present an overview of past and ongoing strategies to inhibit oncogenic Ras in cancer. Since approaches to directly target mutant Ras have not been successful, most efforts have focused on indirect approaches to block Ras membrane association or downstream effector signaling. While inhibitors of effector signaling are currently under clinical evaluation, genome-wide unbiased genetic screens have identified novel directions for future anti-Ras drug discovery.

Marine natural products: a new wave of drugs?

Abstract: The largely unexplored marine world that presumably harbors the most biodiversity may be the vastest resource to discover novel ‘validated’ structures with novel modes of action that cover biologically relevant chemical space. Several challenges, including the supply problem and target identification, need to be met for successful drug development of these often complex molecules; however, approaches are available to overcome the hurdles. Advances in technologies such as sampling strategies, nanoscale NMR for structure determination, total chemical synthesis, fermentation and biotechnology are all crucial to the success of marine natural products as drug leads. We illustrate the high degree of innovation in the field of marine natural products, which in our view will lead to a new wave of drugs that flow into the market and pharmacies in the future.

Macrocycles in new drug discovery

Abstract: The use of drug-like macrocycles is emerging as an exciting area of medicinal chemistry, with several recent examples highlighting the favorable changes in biological and physicochemical properties that macrocyclization can afford. Natural product macrocycles and their synthetic derivatives have long been clinically useful and attention is now being focused on the wider use of macrocyclic scaffolds in medicinal chemistry in the search for new drugs for increasingly challenging targets. With the increasing awareness of concepts of drug-likeness and the dangers of 'molecular obesity', functionalized macrocyclic scaffolds could provide a way to generate ligand-efficient molecules with enhanced properties. In this review we will separately discuss the effects of macrocyclization upon potency, selectivity and physicochemical properties, concentrating on recent case histories in oncology drug discovery. Additionally, we will highlight selected advances in the synthesis of macrocycles and provide an outlook on the future use of macrocyclic scaffolds in medicinal chemistry.