Juan Bueno

In vitro activity of fluconazole, itraconazole, voriconazole and terbinafine against fungi causing onychomycosis

Background.  Onychomycosis is one of the commonest dermatological diseases worldwide. The antifungal activity of current medications varies, and treatment failure occurs in 25–40% of treated patients.

Microwave induced three-component synthesis and antimycobacterial activity of benzopyrazolo[3,4-b]quinolindiones.

Three series of novel 4-arylbenzo[h]pyrazolo[3,4-b]quinolin-5,6-diones 4, 7 and 9 have been efficiently obtained in good yields by three-component microwave assisted reaction between aminopyrazoles 1 or 6 (both 1-phenyl and 1-H substituted), 2-hydroxynaphthoquinone 2 and benzaldehydes 3. Compounds 4, 7 and 9 have been evaluated against fifteen Mycobacterium spp strains, and six of them have shown antimycobacterial activity. The highest inhibitory activity with MIC ≤2 μg/mL for three of these compounds (4a, 4b and 4g) was related with their highest lipophilicity and lesser polarity within these series.

Anti-Biofilm Drug Susceptibility Testing Methods: Looking for New Strategies against Resistance Mechanism

Biofilm is a reservoir of drug resistant microorganisms that can increase the failure rate of anti-infective therapy and is a public health concern. Antibiofilm drug discovery is necessary for developing new drugs, biocides and wound management protocols. This makes the standardization and implementation of in vitro antibiofilm screening platforms a challenge in the search for new antibiotics, because current antimicrobials are active against planktonic bacteria and have poor diffusion across biofilm matrix. Usually, based in the research topic, the antibiofilm methods have been classified in static and flow depending of continuous supply of nutrients that affect the microbial growth, the final aim of these assays is obtain Minimal Biofilm Inhibitory Concentration (MBIC) and Minimal Biofilm Eradication Concentration (MBEC) values as efficacy parameter of the compound or procedure evaluated, but is very important correlates data from different models in order to give real results of activity. This review aims at describing the initial tools for to establishing an antibiofilm drug discovery-prospecting program.

Antimicrobial Adjuvants Drug Discovery, the Challenge of Avoid theResistance and Recover the Susceptibility of Multidrug-Resistant Strains

Currently, the emergence of multidrug resistant microorganisms as Acinetobacter baumannii and Mycobacterium tuberculosis as well as new drug resistant forms of Neisseria gonorrhoeae in conjunction with the evolving of resistance genes as the KPC (class A Klebsiella pneumoniae) and NDM-1 (New Delhi metallo-β-lactamase 1) carbapenemases are a public health threat that requires great efforts in prevention, treatment and diagnosis. For that reason, the InterAcademy Panel and InterAcademy Medical Panel statement (IAP-IAMP) included in their Global recommendations call for action to tackle antimicrobial resistance under the following item “Encourage industry innovation and public–private collaborative research and development programs for therapeutics, diagnostics, and vaccines”. In this way, the development of novel antimicrobial drugs is not only necessary, is a priority the search and development of new pharmacological strategies for prevent antimicrobial resistance emergence, these strategies should have the ability of improve the current anti-infective therapy in combination, and recuperate the susceptibility of multidrug-resistant strains to the antibiotics. Thereupon, the introduction of screening platforms in a rational in vitro antimicrobial adjuvants drug discovery program is an important approach that will allow the detection of new chemical entities that can inhibit resistant mechanisms specifically and without side effects, looking for increase the microbicidal effect and prevent the development of subsequent mutations to anti-infective therapy. The aim of this review is to explore antibiotic adjuvants as therapeutic plan of action that can be developed for the discovery of new compounds that make bacteria more susceptible to anti-infectives by improving their efficacy.

Antitubercular In Vitro Drug Discovery: Tools for Begin the Search

Tuberculosis (TB) caused by Mycobacterium tuberculosis continues being a big public health problem around the world. The total number of cases of TB worldwide in 2009 was 9.4 million of which 1.8 million died of this disease, reported as the higher in history (Lawn & Zumla, 2011), World Health Organization (WHO) estimates that the one third of global population is infected latently by M. tuberculosis (LTBI), however 10% will develop active disease (Zumla et al., 2011). Although several strategies and programs have been implemented and anti TB drugs have been available for 50 years, many TB patients are not diagnosed and treated at time (Ghanashyam, 2011; Sosnik et al., 2010). These mismanaged patients, with non-optimal treatments are the principal source of multidrugresistant TB (MDR-TB), which is resistant to the first line drugs isoniazid and rifampicin, as well as extensive drug resistant TB (XDR-TB), that in addition of isoniazid and rifampicin is resistant to any fluoroquinolone and any aminoglycoside second line anti TB injectable drugs (Koul et al., 2011). Other aspect that aggravates the situation is the coinfection with Human Immunodeficiency Virus (HIV) disease, which increases the TB incidence rates three to five times and affected 1.1 million of TB cases in 2009 (Lawn & Zumla, 2011).

Biosensors in Antimicrobial Drug Discovery: Since Biology until ScreeningPlatforms

Antimicrobial drug resistance is a current public health problem, which is compounded by the misuse of antibiotics in medical practice and the emergence of Multidrug-Resistant (MDR) microorganisms. Therefore it is necessary to develop new anti-infective drugs and implement new methodologies able to establish the Antimicrobial Susceptibility (AST) in field and the point-of-care. In this sense biosensors is a promising technology that can detect MDR strains and small molecules in various samples, these devices have the advantages that can be miniaturized for obtain portability, rapidity, and cost-effectiveness. The aim of this work is to present the applications of biosensors technology in antimicrobial drug discovery, since cell based biosensors and cell culture on chips, considering metabolic interactions of the microbial world and the pharmacological response to be inhibited by compounds with promising activity with the end of design antimicrobial drug screening platforms robust, automatable and reproducible.

Antifungal activity and chemical composition of the essential oils of Lippia alba (Miller) N.E Brown grown in different regions of Colombia.

Abstract The essential oils from Lippia alba (Miller) N.E Brown (Verbenaceae Family) collected in different regions of Colombia were obtained by microwave-assisted hydrodistillation. Their chemical compositions were determined by GC and GC/MS. Two chemotypes were distinguished, characterized by carvone and citral as main constituents. Antifungal activity of the essential oils was determined following the standard microdilution protocols AFST-EUCAST for C. krusei and C. parasilopsis, and CLSI-M38A for Aspergillus fumigatus and A. flavus. The essential oils obtained from both L. alba chemotypes showed antifungal activity.

Metabolomics in Antimicrobial Drug Discovery: The Success of the Chemical Diversity

Metabolic networks are an expression of the functionality in biological systems, with the study of metabolomics is possible to obtain data about the physiological state of organisms interacting with various environmental factors, equally develop treatment strategies that reverse the disease. Currently, the metabolomics are a promising tool in drug discovery; because can elucidate drug targets, identify new sources of bioactive compounds and lead the development of new trends for drug production as well as select patients for clinical trials and monitor their health status. In this commentary article will be explored the metabolomics as perhaps the more interesting set of techniques able to influence various fields, and most expectancy to use it to cross the valley of death between basic science and application, especially in a public health threat as is antimicrobial resistance.

ACTIVIDAD IN VITRO ANTI-CANDIDA Y ANTI-ASPERGILLUS DE ACEITES ESENCIALES DE PLANTAS DE LA FAMILIA PIPERACEAE

Plants of the Piperaceae family have been used with medicinal purposes in different regions around the world. In vitro antifungal activity of 10 essential oils from species of Piper genus were measured by determination of minimum inhibitory concentration (MIC) against A. flavus fungi ATCC 204304 and A. fumigatus ATCC 204305 following the standard protocol CLSI M38-A. In addition, Candida krusei ATCC 6258 and C. parapsilosis ATCC 22019 were evaluated with modified protocol M27-A2. The essential oil with the most antifungal activity was Piper sanctifelisis for C. krusei (CMI: 125 µg/mL).

Evaluación de la actividad anti-candida y anti-aspergillus de aceites esenciales de lippia alba (miller) n.e brown quimiotipo carvonalimoneno y su asociación con sus componentes mayoritarios.

The plants are source of active secondary metabolites and the essential oils of Lippia alba species have been showed antifungal activity in vitro recently. In this study, antifungal activity of five essential oils of Lippia alba species chemotype carvone- limonene from different parts of the country were evaluated by determining the minimum inhibitory concentration (MIC) following standard microdilution method protocols AFST-EUCAST EUCAST for glucose fermentation yeasts and CLSI-M38A for filamentous fungi. It was found that the most active oil was obtained of Lippia alba from Flandes-Tolima with values of MIC of 0,004 ±0,0%v/v for A. fumigatus and 0,036±0,021 for C. krusei. Essential oils of Lippia alba more active showed an association with its majority components limonene, carvone and bicyclosesquiphellandrene to approximate rate of 18/27/27 respectively .