Activitatea antifungică a fenoxitiazolcloralului

Background. Fungal susceptibility is an important criteria in design of new antimycotic drugs. The parameters of susceptibility are the minimum inhibitory concentration (MIC) and the minimum fungicidal concentration (MCF). Objective of the study. Susceptibility testing of Aspergillus fumigatus (A.fum.), Aspergillus versicolor (A.v.) and Candida albicans (C.alb.) to phenoxythiazolcloralum (MF- 10). Material and Methods. Aspergillus and Candida species; ketoconazole standard (st.); bifonazole (st); nystatin (st); MF-10 (for analysis); b-cyclodextrine - MF-10 complex (βCD:MF-10 ). NCCLS M27 methodology to C.alb. and NCCLS M38 – to A.fum and A.v. Results. Compared to ketoconazole (st), MIC of MF-10 is 18,4% less on A.fum and A.v. cultures; MCF 34,04% less (A.fum.) and 3,12% less(A.v.). MIC is 33% less and MFC- 3% less than bifonazole (st) on A.fum și A.v culture. Microbiological tests on C.alb. demonnstrated that MF-10 is 25% more active than nystatin (st.), and βCD:MF-10 complex (1:1)- by 56.25%. Conclusion. According to the obtained MIC and MCF values, MF-10 and βCD:MF-10 (1:1) have better antimycotic activity than standards. These findings will be used in the design of new antimycotic local drugs. Introducere. Sensibilitatea fungilor este un criteriu cheie în proiectarea noilor medicamente antimicotice. Parametrii ce descriu această sensibilitate sunt concentrația minimă inhibitorie (CMI) și concentrația minimă fungicidă (CMF). Scopul lucrării. Determinarea sensibilității speciilor: Aspergillus fumigatus (A.fum.), Aspergillus versicolor (A.v.) și Candida albicans (C.alb.) față de fenoxitiazolcloral (MF-10). Material și Metode. Culturi de fungi; ustensile de laborator; ketoconazol standard (st.); bifonazol (st); nistatină (st); MF-10 (pentru analiză); complexul MF-10 cu β-ciclodextrine (β-CD:MF-10 ). Metode standardizate NCCLS M27 pentru determinarea sensibilității C. alb. și NCCLS M38 pentru A.fum și A.v. Rezultate. În raport cu ketoconazolul, indicele CMI al MF-10 este cu 18,4% mai mic față de culturile A.fum și A.v., iar CMF- mai mic cu 34,04% (A.fum.) și 3,12%(A.v.). În raport cu bifonazolul, CMI este cu 1/3 mai mic, iar CMF- cu 3% pentru A.fum și A.v. Testele antifungice față de C.alb. au demonstrat că MF-10 este cu 25% mai activ decât nistatina (st.), iar complexul β-CD:MF- 10 (1:1)- cu 56,25%. Concluzii. Conform indicilor MIC și MCF, substanțele MF-10 și βCD:MF-10 (1:1) posedă o activitate terapeutică mai pronunțată decât substanțele standard. Acest studiu argumentează proiectarea unui nou medicament antimicotic cu acțiune locală

Antimycotic activity of phenoxythiazolchloralum

Department of Pharmaceutical and Toxicological Chemistry, Drug Scientific Center, Nicolae Testemitanu State University of Medicine and Pharmacy, Chisinau, the Republic of Moldova, Laboratory of Organic Synthesis and Biopharmaceuticals, Institute of Chemistry, Chisinau, the Republic of Moldova, The 75th anniversary of Nicolae Testemitanu State University of Medicine and Pharmacy of the Republic of Moldova (1945-2020)Background: The therapeutic options in invasive candidiasis and aspergillosis are limited and don’t provide expected results. Introducing a new drug in the therapeutic practice can improve the quality of life of immunocompromised patients. The aim of this research is to study the antimycotic activity of new substance phenoxithiazolchloralum (MF-0010) on Aspergillus spp., Candida albicans, and Saccharomyces cerevisiae. Material and methods: Phenoxythiazolchoralum has been kindly offered by the Institute of Chemistry. The standards were offered by Nicolae Testemitanu State University of Medicine and Pharmacy. Antifungal activity of the phenoxythiazolchloralum against Aspergillus spp. was evaluated by microdilution method. The successive double dilution method was used for determination of in vitro susceptibility against Candida albicans, and Saccharomyces cerevisiae. Results: For the first time, it was studied in vitro susceptibility of MF-0010 against Aspergillus spp., Candida albicans, Saccharomyces cerevisiae. With at least 0.05 μM/ml difference of MF-0010 MIC value from standards, it can be considered quite more potent than ketoconazole and bifonazole against Aspergillus fumigatus, Aspergillus versicolor, Aspergillus ochramensis. The MIC/MCF ratios of MF-0010 are lower than nistatine ones with 0.08 μMol for both pathogens: Candida albicans, and Saccharomyces cerevisiae. Conclusions: All analyzed pathogens were susceptible to MF-0010. According to experimental data on Aspergillus spp., the antimycotic activity of MF-0010 is quite better than the standards one. The MIC/MCF ratios showed in vitro significant susceptibility of MF-0010 against Candida albicans

Sinteza și studiul preclinic al unui nou derivat nesaturat al 1,2,4-triazolului cu acțiune antifungică

Background. Dermatomycoses are the most common fungal infections. Azoles and their derivatives are drugs intended for the treatment of fungal infections, the basic criterion in their synthesis being the sensitivity of fungi. Objective of the study. Synthesis, preclinical analysis study, determination of species sensitivity: Aspergillus fumigatus (A.fum.) and Aspergillus versicolor (A.v.) compared to Nitrotriazon – antifungal triazole derivative. Material and Methods. IR, UV spectroscopy, CSS, HPLC. NCCLS M38 standardized methods for determining the sensitivity of A.fum., A.v. Standardized fungal species; standard ketoconazole (st.); bifonazole (st); Nitrotriazon – for analysis. Results. The method of obtaining the compound Nitrotriazon was optimized and its physico-chemical properties were studied. The minimum inhibitory concentration (MIC) and the minimum fungicidal concentration (MFC) in mM were determined. For Nitrotriazon: A.fum. and A.v: MIC=0,10 and MFC=0,19; Ketoconazol: A.fum. and A.v: MIC=0,38 and MFC=0,94; Bifonazol: A.fum: MIC=0,48; A.v: MIC=0,32; And MFC=0,64 for A.fum, A.v. Conclusion. The MIC and MFC indices indicate that Nitrotriazone possesses a more pronounced therapeutic activity than standard substances. Long-term azole therapy causes resistance, so obtaining new antifungal agents with minimal side effects remains relevant. Introducere. Dermatomicozele sunt cele mai răspândite infecții fungice. Azolii și derivații lor sunt medicamente destinate tratamentului infecțiilor fungice, criteriul de bază în sinteza acestora fiind sensibilitatea fungilor. Scopul lucrării. Sinteza, studiul preclinic de analiză, determinarea sensibilității speciilor: Aspergillus fumigatus (A.fum.) și Aspergillus versicolor (A.v.) față de Nitrotriazon–derivat triazolic antifungic. Material și Metode. CSS, HPLC, spectroscopie în IR, UV. Metode standardizate NCCLS M38 pentru determinarea sensibilității A.fum., A.v. Specii de fungi standardizate; ketoconazol standard (st.); bifonazol (st); Nitrotriazon–pentru analiză. Rezultate. A fost optimizată metoda de obținere a compusului Nitrotriazon și studiate proprietățile fizico-chimice ale acestuia. A fost determinată concentrația minimă inhibitorie (CMI) și concentrația minimă fungicidă (CMF), în mM. Pentru Nitrotriazon: A.fum. și A.v: CMI=0,10 și CMF=0,19; Ketoconazol: A.fum. și A.v: CMI=0,38 și CMF=0,94; Bifonazol: A.fum: CMI=0,48; A.v: CMI=0,32; Iar CMF=0,64 pentru A.fum, A.v. Concluzii. Indicii CMI și CMF denotă că Nitrotriazonul posedă o activitate terapeutică mai pronunțată decât substanțele standard. Terapia pe termen lung cu azoli provoacă rezistență, astfel obținerea noilor agenți antifungici cu minime efecte adverse rămâne actuală

Antimycotic activity of phenoxythiazolchloralum

Department of Pharmaceutical and Toxicological Chemistry, Drug Scientific Center Nicolae Testemitanu State University of Medicine and Pharmacy, Chisinau, the Republic of Moldova, Laboratory of Organic Synthesis and Biopharmaceuticals, Institute of Chemistry, Chisinau, the Republic of Moldova, Congresul consacrat aniversării a 75-a de la fondarea Universității de Stat de Medicină și Farmacie „Nicolae Testemițanu” din Republica Moldova, Ziua internațională a științei pentru pace și dezvoltareIntroduction. The therapeutic options in invasive candidiasis and aspergillosis are limited and don’t provide expected results. Introducing a new drug in the therapeutic practice can improve the quality of life of immunocompromised patients. The compound have poor solubility in polar solvents (water, methanol, ethanol, acetonitrile, acetone) and low bioavailability that limits the use as antitubercular agent. But, presence of the azole ring (pharmacophore group of azole antimycotic drug) suggests that the studied substance may have antimycotic activity. Purpose. The aim is to study the antimycotic activity of new substance phenoxithiazolchloralum (MF0010) on Aspergillus spp., Candida albicans, and Saccharomyces cerevisiae. Material and methods. Aspergillus spp. For the evaluating of the antifungal activity of the phenoxythiazolchloralum compound against Aspergillus spp. it was used the microdilution method described by E. Stingaci et al.(Stingaci E, Zveaghinteva M, Pogrebnoi S, Lupascu L, Valica V, Uncu L, Smetanscaia A, Drumea M, Petrou A, Ciric A, Glamoclija J, Sokovic M, Kravtsov V, Geronikaki A, Macaev F. New vinyl-1,2,4-triazole derivatives as antimicrobial agents: Synthesis, biological evaluation and molecular docking studies. Bioorganic & Medicinal Chemistry Letters. 2020;30(17). DOI:10.1016/j.bmcl.2020.127368). Candida albicans and Saccharomyces cerevisiae For the evaluating of the antifungal activity for Candida albicans, and Saccharomyces cerevisiae was used the successive double dilution method (NCCLS M27). Results. For the first time, it was studied in vitro susceptibility of MF-0010 against A. fumigatus, A. versicolor, A. ochramensis and A. niger. The MIC and MFC values of MF-0010 against Aspergillus spp. ranged from 0.23μM/ml – 0.62μM/ml and 0,62μM/ml –1.24μM/ml, respectively. The highest values of MIC and MCF of MF-0010 is related to A. niger. Thus, the use of MF-0010 against this pathogen is not appropriate. With at least 0.05 μM/ml difference of MICs from standards, MF-0010 can be considered quite more potent than ketoconazole and bifonazole. The MIC/MCF ratios of MF-0010 for inhibition of Candida albicans, Saccharomyces cerevisiae of are lower than nistatine ones with 0.08 μMol for both pathogens. Thus, we can conclude that MF-0010 is more potent active molecule than nistatine against Candida albicans. Conclusions. In this study, we found that all analyzed pathogens were susceptible to MF-0010. According to experimental data, the antimycotic activity of MF-0010 is quite better than the standards one. The MIC and MCF values of MF-0010 show a good potency against Candida albicans, and new studies are warranted in order to design optimized formulations, to analyse in vivo efficacy and quality assurance of formulations

Characterization of Propolis from Moldova's Central Region: Chemical Composition, Antioxidant and Antimicrobial Properties

The chemical composition, antioxidant and antimicrobial activity of propolis ethanolic and water-ethanolic extracts from the central zone of Moldova have been investigated by GC-MS and liquid chromatography. There were found 20 amino acids, of which the most abundant are glutamic acid, alanine, leucine and isoleucine. The main constituents of the alcoholic extract are pinocembrin, n-heptacosan and naringenin. The aqueous-alcoholic extract was characterized by the content of sakuranin, 4-methoxy sakuranetin, caryophylline oxide, isocaryophylline oxide, trans-longipinocarveol. The propolis extracts exhibited strong antioxidant (53.7 mg ascorbic acid eq./g extract or 113.4 mg Trolox eq./g extract and 87.5 mg ascorbic acid eq./g extract or 162 mg Trolox eq./g extract for ethanol, and water-ethanol extract, respectively) and antimicrobial activity (from 0.0055 up to 0.07%), suggesting their potential as natural agents for therapeutic use

Determinarea toxicităţii acute a unor noi compuşi chimici cu proprietăţi antituberculoase

La Institutul de Chimie al AŞM au fost sintetizaţi compusi, principalele substanţe active ale cărora reprezintă derivaţi ai oxadiazolilor. Datele preliminare ale testărilor in vitro au determinat activitatea inhibitorie asupra creşterii coloniilor M.tuberculosis. În cadrul proiectului „De la compuşi naturali la analogii lor şi spre evaluarea preclinică a noilor compuşi cu proprietăţi antituberculoase” la Centrul Ştiinţific al Medicamentului al IP USMF „Nicolae Testemiţanu” a fost evaluată toxicitatea acută a 7 compuşi sintetizaţi. Pentru compuşii MF51, MF14 s-a constatat toxicitatea minimă, ei fiind plasaţi în clasa de toxicitate 5 conform TG 423 Acute Toxic Class Method (OECD)

Design, synthesis, computational and biological evaluation of new anxiolytics

Abstract New anxiolytics have been discovered by prediction of biological activity with computer programs PASS and DE DEREK for a heterogeneous set of 5494 highly chemically diverse heterocyclic compounds (thiazoles, pyrazoles, isatins, a fused imidazoles and others). The majority of tested compounds exhibit the predicted anxiolytic effect. The most potent activity was found in 2 (4 nitro phenyl) 3 (4 phenylpiperazinomethyl)imidazo[1,2 a]pyridine 8, 1 [(4 bromophenyl) 2 oxoethyl] 3 (1,3 dioxolano) 2 indolinone 3, 5 hydroxy 3 methoxycarbonyl 1 phenylpyrazole 5 and 2 (4 fluorophenyl) 3 (4 methylpiperazinomethyl)imidazo[1,2 a]pyridine 7. The application of the computer assisted approach significantly reduced the number of synthesized and tested compounds and increased the chance of finding new chemical entities (NCEs)

SYNTHESIS AND CHARACTERIZATION OF [(5-MERCAPTO-1,3,4-OXADIAZOL-2-YL)ARYL]-3,5-DIARYL-4,5-DIHYDRO-1H-PYRAZOLE-1-CARBOTHIOAMIDES

The synthesis and characterization of [(5-mercapto-1,3,4-oxadiazol-2-yl)aryl]-3,5-diaryl-4,5-dihydro-1Hpyrazole-1-carbothioamides - derivatives of pyrazolines and 5-[4(3)-isothiocyanatophenyl]-2-thio-1,3,4-oxadiazoles were realized. The synthesized compounds, are crystalline substances, stable in storage and when exposed to air and light

MOLECULAR CONCEPTS OF MACROPHAGE TARGETING

Macrophages play an important role in the pathological development of different diseases. Therefore, macrophage targeting represents an important challenge in design of new medicines. This review gives a general presentation of small molecule-recognition concepts used for macrophage targeting. It describes mechanisms and systems for macrophage-targeted delivery, their obtaining and application

NEW ROOM TEMPERATURE LIQUIDS: SYNTHESIS AND CHARACTERIZATION

Room temperature ionic liquids (ILs) have been recognized as a new generation of solvents for “green chemistry” and represent remarkably promising classes of technologically useful and fundamentally interesting materials [1-6]. Most of them are quaternary imidazolium cations with inorganic counterions. Cation in these salts is appended to the organic group (usually saturated hydrocarbon fragments). However, some problems regarding the functionalization [2,7], coordination properties [4] of ILs still remain to be solved. It seems to us that functionalization of imidazoles by ethylcarbonitrile, allyl, 2,3-epoxypropyl fragments will lead to new properties of synthesized ILs. There are no literature data on use of 2-(1H-1-imidazolyl)ethylcarbonitrile 4 for synthesis of imidazolium salts with ILs properties