An Overview on Synthetic and Medicinal Perspectives of [1,2,4]Triazolo[1,5-a]pyrimidine Scaffold.

[1,2,4]Triazolo[1,5-a]pyrimidine is an important heterocyclic scaffold known to have a wide range of pharmacological activities such as anticancer, antimicrobial, anti-tubercular, CB2 cannabinoid agonists, feticide, and adenosine antagonists. Several clinical trials and marketed drugs such as Trapidil, Essramycin, Pyroxsulam, DSM-265, Flumetsulam, GNF-6702, and Cevipabulin indicate the potential of [1,2,4]triazolo[1,5-a]pyrimidine moiety with various functional groups in medicinal chemistry. Herein, we represent a concise report focusing on the synthetic strategies used for diversely substituted [1,2,4]triazolo[1,5-a]pyrimidine analogs and their pharmacological applications. To the best of our knowledge, since 1980, we are the first to write a review on this emerging scaffold, which reveals the synthetic strategies, and pharmacological activities of differently substituted [1,2,4]triazolo[1,5-a]pyrimidine with special emphasis on structure-activity relationship studies.

An appraisal on synthetic and pharmaceutical perspectives of pyrazolo[4,3-d]pyrimidine scaffold.

Pyrazolo[4,3-d]pyrimidine, a fused heterocycle bearing pyrazole and pyrimidine portions has gained a significant attention in the field of bioorganic and medicinal chemistry. Pyrazolo[4,3-d]pyrimidine derivatives have demonstrated numerous pharmacological activities particularly, anti-cancer, anti-infectious, phosphodiesterase inhibitors, adenosine antagonists and cytokinin antagonists etc. This review extensively unveils the synthetic and pharmacological diversity with special emphasis on structural variations around pyrazolo[4,3-d]pyrimidine scaffold. This endeavour has thus uncovered the medicinal worthiness of pyrazolo[4,3-d]pyrimidine framework. To the best of our knowledge this review is the first compilation on synthetic, medicinal and structure activity relationship (SAR) aspects of pyrazolo[4,3-d]pyrimidines since 1956.

Oxo- and thiooxo-imidazo[1,5-c]pyrimidine molecule library: beyond their interest in inhibition of Brucella suis histidinol dehydrogenase, a powerful protection tool in the synthesis of histidine analogues.

Histidinol dehydrogenase (HDH) has been established as a virulence factor for the human pathogen bacterium Brucella suis. Targeting such a virulence factor is a relevant anti-infectious approach as it could decrease the frequency of antibiotic resistance appearance. In this paper, we describe the synthesis of a family of oxo- and thioxo-imidazo[1,5-c]pyrimidines, potential enzyme inhibitors. Beyond their anti-HDH activity, the synthesis approach of these molecules, never described before, is highly original and these oxo- and thioxo- derivatives can improve dramatically the efficiency of the histidine protection pathway for the synthesis of histidine analogues.

On the potential role of naturally occurring carboxylic organic acids as anti-infective agents: opportunities and challenges.

Carboxylic organic acids are intermediates of central carbon metabolic pathways (e.g. acetic, propionic, citric, and lactic acid) long known to have potent antimicrobial potential, mainly at acidic pHs. The food industry has been leveraging those properties for years, using many of these acids as preservatives to inhibit the growth of pathogenic and/or spoilage fungal and bacterial species. A few of these molecules (the most prominent being acetic acid) have been used as antiseptics since Hippocratic medicine, mainly to treat infected wounds in patients with burns. With the growth of antibiotic therapy, the use of carboxylic acids (and other chemical antiseptics) in clinical settings lost relevance; however, with the continuous emergence of multi-antibiotic/antifungal resistant strains, the search for alternatives has intensified. This prospective article raises awareness of the potential of carboxylic acids to control infections in clinical settings, considering not only their previous exploitation in this context (which we overview) but also the positive experience of their safe use in food preservation. At a time of great concern with antimicrobial resistance and the slow arrival of new antimicrobial therapeutics to the market, further exploration of organic acids as anti-infective molecules may pave the way to more sustainable prophylactic and therapeutic approaches.

Advances of Cobalt Nanomaterials as Anti-Infection Agents, Drug Carriers, and Immunomodulators for Potential Infectious Disease Treatment.

Infectious diseases remain the most serious public health issue, which requires the development of more effective strategies for infectious control. As a kind of ultra-trace element, cobalt is essential to the metabolism of different organisms. In recent decades, nanotechnology has attracted increasing attention worldwide due to its wide application in different areas, including medicine. Based on the important biological roles of cobalt, cobalt nanomaterials have recently been widely developed for their attractive biomedical applications. With advantages such as low costs in preparation, hypotoxicity, photothermal conversion abilities, and high drug loading ability, cobalt nanomaterials have been proven to show promising potential in anticancer and anti-infection treatment. In this review, we summarize the characters of cobalt nanomaterials, followed by the advances in their biological functions and mechanisms. More importantly, we emphatically discuss the potential of cobalt nanomaterials as anti-infectious agents, drug carriers, and immunomodulators for anti-infection treatments, which might be helpful to facilitate progress in future research of anti-infection therapy.

In vitro Antimicrobial Activity of Essential Oil Extracted from Leaves of Leoheo domatiophorus Chaowasku, D.T. Ngo and H.T. Le in Vietnam.

:The present study aimed to determine the antimicrobial activity and chemical composition of leaves-extracted essential oil of Leoheo domatiophorus Chaowasku, D.T. Ngo and H.T. Le (L. domatiophorus), including antibacterial, antimycotic, antitrichomonas and antiviral effects. The essential oil was obtained using hydrodistillation, with an average yield of 0.34 ± 0.01% (v/w, dry leaves). There were 52 constituents as identified by GC/MS with available authentic standards, representing 96.74% of the entire leaves oil. The essential oil was comprised of three main components, namely viridiflorene (16.47%), (-)-δ-cadinene(15.58%) and γ-muurolene (8.00%). The oil showed good antimicrobial activities against several species: Gram-positive strains: Staphylococcus aureus (two strains) and Enterococcus faecalis, with Minimum Inhibitory Concentration (MIC) and Minimum Lethal Concentration (MLC) values from 0.25 to 1% (v/v); Gram-negative strains such as Escherichia coli (two strains), Pseudomonas aeruginosa (two strains) and Klebsiella pneumoniae, with MIC and MLC values between 2% and 8% (v/v); and finally Candida species, having MIC and MLC between 0.12 and 4% (v/v).Antitrichomonas activity of the oil was also undertaken, showing IC50, IC90 and MLC values of 0.008%, 0.016% and 0.03% (v/v), respectively, after 48h of incubation. The essential oil resultedin being completely ineffective against tested viruses, ssRNA+ (HIV-1, YFV, BVDV, Sb-1, CV-B4), ssRNA- (hRSVA2, VSV), dsRNA (Reo-1), and dsDNA (HSV-1, VV) viruses with EC50 values over 100 µg/mL. This is the first, yet comprehensive, scientific report about the chemical composition and pharmacological properties of the essential oil in L. domatiophorus.

Lipid Membranes as Key Targets for the Pharmacological Actions of Ginsenosides.

In this review, we will focus on the activity of ginsenosides on membranes and their related effects, from physicochemical, biophysical, and pharmacological viewpoints. Ginsenosides are a class of saponins with a large structural diversity and a wide range of pharmacological effects. These effects can at least partly be related to their activity on membranes which results from their amphiphilic character. Some ginsenosides are able to interact with membrane lipids and associate into nanostructures, making them possible adjuvants for vaccines. They are able to modulate membrane biophysical properties such as membrane fluidity, permeability or the formation of lateral domains with some degree of specificity towards certain cell types such as bacteria, fungi, or cancer cells. In addition, they have shown antioxidant properties which protect membranes from lipid oxidation. They further displayed some activity on membrane proteins either through direct or indirect interaction. We investigate the structure activity relationship of ginsenosides on membranes and discuss the implications and potential use as anticancer, antibacterial, and antifungal agents.

An insight on synthetic and medicinal aspects of pyrazolo[1,5-a]pyrimidine scaffold.

Pyrazolo[1,5-a]pyrimidine scaffold is one of the privileged hetrocycles in drug discovery. Its application as a buliding block for developing drug-like candidates has displayed broad range of medicinal properties such as anticancer, CNS agents, anti-infectious, anti-inflammatory, CRF1 antagonists and radio diagnostics. The structure-activity relationship (SAR) studies have acquired greater attention amid medicinal chemists, and many of the lead compounds were derived for various disease targets. However, there is plenty of room for the medicinal chemists to further exploit this privileged scaffold in developing potential drug candidates. The present review briefly outlines relevant synthetic strategies employed for pyrazolo[1,5-a]pyrimidine derivatives. It also extensively reveals significant biological properties along with SAR studies. To the best of our understanding current review is the first attempt made towards the compilation of significant advances made on pyrazolo[1,5-a]pyrimidines reported since 1980s.