A new class of anti-MRSA and anti-VRE agents: preparation and antibacterial activities of indole-containing compounds

A new class of indole-containing compounds were prepared by the use of three component reaction and their in vitro antibacterial activities (MIC) were evaluated against Staphylococcus aureus and Enterococcus faecium including MRSA and VRE.     

Synthesis and in vitro activity of dicationic bis-benzimidazoles as a new class of anti-MRSA and anti-VRE agents

A new class of novel bis-benzimidazole diamidine compounds have been synthesized and evaluated for in vitro antibacterial activities, including drug-resistant bacterial strains. Anti-MRSA and anti-VRE activities of the most potent compound 1 were more active than Vancomycin. The mechanism of action for this class of compounds appears to be different from existing antibiotics. Bis-benzimidazole diamidine compounds have potential for further investigation as a new class of potent anti-MRSA and anti-VRE agents.     

Challenges and opportunities in the development of metal-based anticancer theranostic agents

Around 10 million fatalities were recorded worldwide in 2020 due to cancer and statistical projections estimate the number to increase by 60% in 2040. With such a substantial rise in the global cancer burden, the disease will continue to impose a huge socio-economic burden on society. Currently, the most widely used clinical treatment modality is cytotoxic chemotherapy using platinum drugs which is used to treat variety of cancers. Despite its clinical success, critical challenges like resistance, off-target side effects and cancer variability often reduce its overall therapeutic efficiency. These challenges require faster diagnosis, simultaneous therapy and a more personalized approach toward cancer management. To this end, small-molecule ‘theranostic’ agents have presented a viable solution combining diagnosis and therapy into a single platform. In this review, we present a summary of recent efforts in the design and optimization of metal-based small-molecule ‘theranostic’ anticancer agents. Importantly, we highlight the advantages of a theranostic candidate over the purely therapeutic or diagnostic agent in terms of evaluation of its biological properties.     

Molecular design of anti-MRSA agents based on the anacardic acid scaffold

A series of anacardic acid analogues possessing different side chains viz. phenolic, branched, and alicyclic were synthesized and their antibacterial activity tested against methicillin-resistant Staphylococcus aureus (MRSA). The maximum activity against this bacterium occurred with the branched side-chain analogue, 6-(4',8'-dimethylnonyl)salicylic acid, and the alicyclic side-chain analogue, 6-cyclododecylmethyl salicylic acid, with the minimum inhibitory concentration (MIC) of 0.39 microg/mL, respectively. This activity was superior to that of the most potent antibacterial anacardic acid isolated from the cashew Anacardium occidentale (Anacardiaceae), apple and nut, that is, the 6-[8'(Z),11'(Z),14'-pentadecatrienyl]salicylic acid.     

Penicillin-bound polyacrylate nanoparticles: restoring the activity of beta-lactam antibiotics against MRSA

This report describes the preparation of antibacterially active emulsified polyacrylate nanoparticles in which a penicillin antibiotic is covalently conjugated onto the polymeric framework. These nanoparticles were prepared in water by emulsion polymerization of an acrylated penicillin analogue pre-dissolved in a 7:3 (w:w) mixture of butyl acrylate and styrene in the presence of sodium dodecyl sulfate (surfactant) and potassium persulfate (radical initiator). Dynamic light scattering analysis and atomic force microscopy images show that the emulsions contain nanoparticles of approximately 40 nm in diameter. The nanoparticles have equipotent in vitro antibacterial properties against methicillin-susceptible and methicillin-resistant forms of Staphylococcus aureus and indefinite stability toward beta-lactamase.     

Optimization of the central linker of dicationic bis-benzimidazole anti-MRSA and anti-VRE agents

A series of bis-benzimidazole diamidine compounds containing different central linkers has been synthesized and evaluated for in vitro antibacterial activities, including drug-resistant bacterial strains. Seven compounds have shown potent antibacterial activities. The anti-MRSA and anti-VRE activities of compound 1h were more potent than that of the lead compound 1a and vancomycin.     

Bradykinin antagonists: new opportunities

The pro-inflammatory, pain producing, and cardiovascular effects of bradykinin B2 receptor activation are well characterized. Bradykinin B1 receptors also produce inflammation and pain. Therefore, antagonists are expected to be anti-inflammatory/analgesic drugs. Other exploitable clinical opportunities may exist. The newly discovered non-peptide B2 receptor antagonists and the equivalent B1 receptor pharmacological agents, which are in the pipeline, are suitable preclinical tools to properly evaluate potential utilities.     

Novel boronic acid derivatives of bis(indolyl) methane as anti-MRSA agents

Towards the search for a new generation of antibiotics to control methicillin-resistant Staphylococcus aureus (MRSA), the design and synthesis of various bis indolyl methane (BIM) derivatives based on their different electron donor and acceptor properties of the substituents have been made, in which boronic acid derivatives of BIM are found to be active against MRSA. The observed evidence with the lead compound reveals their strong anti-MRSA activity, which paves the way of design and further development of a new generation antibiotics.     

海洋微生物学：新机遇，新挑战

海洋占地球表面积的71%,海洋微生物对海洋及人类的生活有重大影响。由于特殊的生存环境,海洋微生物能产生陆栖微生物所不能产生的结构新颖、作用特殊的生物活性物质,有潜力应用于医疗、食品、环境保护等各个领域。海洋微生物研究充满了新的机遇,同时也面临着新的挑战。《微生物学通报》本期推出了"海洋微生物学主题刊",旨在展现我国海洋微生物学研究的最新进展和成果,促进我国海洋微生物学的交流和发展。     

Isocitrate dehydrogenase mutations: new opportunities for translational research

Over the last decade, comprehensive genome-wide sequencing studies have enabled us to find out unexpected genetic alterations of metabolism in cancer. An example is the identification of arginine missense mutations of isocitrate dehydrogenases-1 and -2 (IDH1/2) in glioma, acute myeloid leukemia (AML), chondrosarcomas, and cholangiocarcinoma. These alterations are closely associated with the production of a new stereospecific metabolite, (R)-2-hydroxyglutarate (R-2HG). A large number of follow-up studies have been performed to address the molecular mechanisms of IDH1/2 mutations underlying how these events contribute to malignant transformation. In the meanwhile, the development of selective mutant IDH1/2 chemical inhibitors is being actively pursued in the scientific community and pharmaceutical industry. The present review article briefly discusses the important findings that highlight the molecular mechanisms of IDH1/2 mutations in cancer and provides a current status for development of selective mutant IDH1/2 chemical inhibitors. [BMB Reports 2015; 48(5): 266-270]     

Darwin in mind: new opportunities for evolutionary psychology

Evolutionary Psychology (EP) views the human mind as organized into many modules, each underpinned by psychological adaptations designed to solve problems faced by our Pleistocene ancestors. We argue that the key tenets of the established EP paradigm require modification in the light of recent findings from a number of disciplines, including human genetics, evolutionary biology, cognitive neuroscience, developmental psychology, and paleoecology. For instance, many human genes have been subject to recent selective sweeps; humans play an active, constructive role in co-directing their own development and evolution; and experimental evidence often favours a general process, rather than a modular account, of cognition. A redefined EP could use the theoretical insights of modern evolutionary biology as a rich source of hypotheses concerning the human mind, and could exploit novel methods from a variety of adjacent research fields.     

Drug discovery and development for ageing: opportunities and challenges

The prevention and treatment of late-life dysfunction are the goals of most geriatricians and should be the primary target for discovery and development of new medicines for elderly people. However, the development of new medicines for elderly people will face a number of challenges that are not seen for other patient populations. The burdens of multiple chronic diseases, low physiological reserve and polypharmacy must result in new clinical trials in frail older people with a high expectation of safety and efficacy. The etiology of functional limitations in elderly people is complex and often ascribed to conditions that escape the traditional definition of disease. While our society urgently needs new treatments that can reduce the burden of physical decline among older persons, guidelines on how these treatments should be developed and tested are currently lacking, in part because a consensus has not yet been achieved regarding the identifiable target diseases. New potential indications included sarcopaenia, anorexia of ageing, frailty, mobility disability and reduced functional capacity secondary to hospitalization. The challenges to conducting clinical trials in the elderly should not offset the great opportunity for the development of new medicines to prevent or reverse age-associated changes in body composition and poor functional capacity in the elderly.     

HIV envelope: challenges and opportunities for development of entry inhibitors

The HIV envelope proteins glycoprotein 120 (gp120) and glycoprotein 41 (gp41) play crucial roles in HIV entry, therefore they are of extreme interest in the development of novel therapeutics. Studies using diverse methods, including structural biology and mutagenesis, have resulted in a detailed model for envelope-mediated entry, which consists of multiple conformations, each a potential target for therapeutic intervention. In this review, the challenges, strategies and progress to date for developing novel entry inhibitors directed at disrupting HIV gp120 and gp41 function are discussed.     

新抗菌药物研发进展

细菌对抗菌药的耐药性已成为全球性问题,另一方面,自上个世纪90年代以来,新抗菌药的研发、上市速度明显下降,造成临床无药可用的境地。但近年来国际上研发了一些对耐药菌具抗菌活性的新化合物及进入各期临床试验的新抗菌药。本文对3个新抗菌药telavancin、ceftaroline及fidaxomicin,2011年底在我国上市的替加环素,以及数个进入I到III期新药临床试验的抗菌药进行综述。     

Peptide arrays for kinome analysis: new opportunities and remaining challenges

Phosphorylation is the predominant mechanism of post-translational modification for regulation of protein function. With central roles in virtually every cellular process, and strong linkages with many diseases, there is a considerable interest in defining, and ultimately controlling, kinase activities. Investigations of human cellular phosphorylation events, which includes over 500 different kinases and tens of thousands of phosphorylation targets, represent a daunting challenge for proteomic researchers and cell biologists alike. As such, there is a priority to develop tools that enable the evaluation of cellular phosphorylation events in a high-throughput, and biologically relevant, fashion. Towards this objective, two distinct, but functionally related, experimental approaches have emerged; phosphoproteome investigations, which focus on the sub-population of proteins which undergo phosphorylation and kinome analysis, which considers the activities of the kinase enzymes mediating these phosphorylation events. Within kinome analysis, peptide arrays have demonstrated considerable potential as a cost-effective, high-throughput approach for defining phosphorylation-mediated signal transduction activity. In particular, a number of recent advances in the application of peptide arrays for kinome analysis have enabled researchers to tackle increasingly complex biological problems in a wider range of species. In this review, recent advances in kinomic analysis utilizing peptides arrays including several of the biological questions studied by our group, as well as outstanding challenges still facing this technology, are discussed.