ABSTRACT
The objective of the work was to study the cytotoxic effect of ent-kaurene acid derivatives obtained from Coespeletia moritziana (Sch. Bip. Ex Wedd.) Cuatrec., After analysis by GC/MS, IR and NMR. Isolating: kaurenic acid (I), grandifloric acid (II), 15-α-hydroxy kaurenic acid (III), 15 α-acetoxy-kaur 16-en-19-oic acid (IV), Kaurenol (V); and by hemisynthesis: 15,16-epoxy-17-acetoxy-kauran 19-oic acid (VI), 15-oxo-ent-kaur-16-en-19-oic acid (VIII), ester 2,3,4,6 -15-oxo-kaur-16-en-19-oic acid acetyl α-D-pyranosyl tetra-tetra (VII). Cytotoxicity was tested in human cancer cell lines: uterus (HeLa), lung (A-549), breast (MCF-7), African green monkey kidney non-tumor line (Vero) and human peripheral blood mononuclear cells (CMPS). Compound (I) was active against HeLa, A-549 and Vero. Compounds (II and VIII) showed moderate and good (IC50 ≤ 9 µM) cytotoxicity, respectively, against the five cell lines. Compound (V) showed moderate activity against A-549 and compound (VII), slight cytotoxicity against HeLa and A-549. Results that show the cytotoxic specificity of the isolated kaurenes and derivatives of Coespeletia moritzianaand their therapeutic potential.
El objetivo del trabajo fue estudiar el efecto citotóxico de derivados del ácido ent-kaureno obtenidos de Coespeletia moritziana (Sch. Bip. ex Wedd.) Cuatrec., previo análisis mediante GC/MS, IR y RMN. Aislandose: ácido kaurénico(I), ácido grandiflorénico (II), ácido 15-α-hidroxi kaurénico(III), ácido 15 α-acetoxi-kaur 16-en-19-oico (IV), Kaurenol (V); y por hemisíntesis: ácido 15,16-epoxi-17-acetoxi-kauran 19-oico (VI), ácido15-oxo-ent-kaur-16-en-19-oico (VIII), éster 2,3,4,6-tetra acetil α-D-piranosilo del ácido 15-oxo-kaur-16-en-19-oico (VII). La citotóxicidad fue ensayada en líneas celulares cancerosas humanas: útero (HeLa), pulmón(A-549), mama (MCF-7), línea no tumoral de riñón de mono verde africano (Vero) y células mononucleares humanas de sangre periférica (CMPS). El compuesto (I) resultó activo frente a HeLa, A-549 y Vero. Los compuestos (II y VIII), mostraron moderada y buena (IC50≤9µM) citotoxicidad respectivamente, frente a las cinco líneas celulares. El compuesto (V) presentó moderada actividad frente a A-549 y el (VII), leve citotoxicidad frente a HeLa y A-549. Resultados que evidencian la especificidad citotóxica de los kaurenos aislados y derivados de Coespeletia moritzianay su potencial terapéutico.
Subject(s)
Plant Extracts/pharmacology , Plant Extracts/chemistry , Asteraceae/chemistry , Cell Line, Tumor/drug effects , Diterpenes/isolation & purification , Spectrophotometry, Infrared , Magnetic Resonance Imaging , Chromatography, Thin Layer , Diterpenes, Kaurane , Diterpenes/pharmacology , Gas Chromatography-Mass SpectrometryABSTRACT
The global emergency caused by COVID-19 makes the discovery of drugs capable of inhibiting SARS-CoV-2 a priority, to reduce the mortality and morbidity of this disease. Repurposing approved drugs can provide therapeutic alternatives that promise rapid and ample coverage because they have a documented safety record, as well as infrastructure for large-scale production. The main protease of SARS-CoV-2 (Mpro) is an excellent therapeutic target because it is critical for viral replication; however, Mpro has a highly flexible active site that must be considered when performing computer-assisted drug discovery. In this work, potential inhibitors of the main protease (Mpro) of SARS-Cov-2 were identified through a docking-assisted virtual screening procedure. A total of 4384 drugs, all approved for human use, were screened against three conformers of Mpro. The ligands were further studied through molecular dynamics simulations and binding free energy analysis. A total of nine currently approved molecules are proposed as potential inhibitors of SARS-CoV-2. These molecules can be further tested to speed the development of therapeutics against COVID-19.
Subject(s)
Betacoronavirus/enzymology , Coronavirus Infections/drug therapy , Drug Evaluation, Preclinical , Drug Repositioning , Pneumonia, Viral/drug therapy , Protease Inhibitors/pharmacology , Viral Nonstructural Proteins/antagonists & inhibitors , Antiviral Agents/chemistry , Antiviral Agents/pharmacology , Betacoronavirus/drug effects , COVID-19 , Coronavirus 3C Proteases , Cysteine Endopeptidases/chemistry , Cysteine Endopeptidases/metabolism , Humans , Molecular Dynamics Simulation , Pandemics , Protease Inhibitors/chemistry , Protein Conformation , SARS-CoV-2 , Viral Nonstructural Proteins/chemistry , Viral Nonstructural Proteins/metabolismABSTRACT
Introduction. Biological adhesives and effective topical therapeutic agents that improve wound healing are urgently required for the treatment of chronic ulcers. A biodegradable adhesive based on a carbohydrate polymer with zinc oxide (CPZO) was shown to possess anti-inflammatory activity and enhance wound healing, but its bactericidal activity was unknown.Aim. To investigate the bactericidal activity of CPZO against bacteria commonly present as infectious agents in chronic wounds.Methodology. We examined the bactericidal activity of CPZO against three biofilm-producing bacteria (Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa) through three strategies: bacterial suspension, biofilm disruption and in vitro wound biofilm model.Results. In suspension cultures, CPZO had direct, potent bactericidal action against S. aureus within 24 h, whereas E. coli took 7 days to be eliminated. By contrast, P. aeruginosa survived up to 14 days with CPZO. CPZO had biofilm disruption activity against clinical isolates of S. aureus in the anti-biofilm test. Finally, in the in vitro wound biofilm model, CPZO dramatically reduced the bacterial viability of S. aureus and P. aeruginosa.Conclusions. Together with its previously shown anti-inflammatory properties, the bactericidal activity of CPZO gives it the potential to be a first-line therapeutic option for chronic various ulcers and, possibly, other chronic ulcers, preventing or controlling microbial infections, and leading to the healing of such complicated chronic ulcers.
Subject(s)
Anti-Bacterial Agents/pharmacology , Bacteria/drug effects , Bacterial Infections/drug therapy , Carbohydrates/pharmacology , Polymers/pharmacology , Wound Healing/drug effects , Zinc Oxide/pharmacology , Bacterial Infections/microbiology , Biofilms/drug effects , Humans , Microbial Sensitivity Tests/methodsABSTRACT
In this paper, results obtained upon treatment of the methyl ester of ent-kaur-16-en-19-oic acid (1b) with lead tetra-acetate under reflux in glacial acetic acid solution and an argon atmosphere are described. After 30 minutes reflux, GC-MS analysis of the product indicated the presence of three substances, the initial compound (1b, 7 %), the methyl ester of ent-kaur-16-en-15-O-acetyl-19-oic acid (2a, C23H3004, 45 %), and its isomer, the methyl ester of ent-kaur-15-en-17- 0-acetyl-19-oic acid (3a, 47 %). Flash chromatography over silica gel containing 20% AgNO3 yielded 2b (456 mg), which was identified by direct comparison with an authentic sample, and 3a (472 mg), whose structure was established by uni- and bi-dimensional NMR analysis. Hydrolysis of 3a with dry ammonia in MeOH yielded the methyl ester of ent-kaur-15-en-17-hydroxy-19-oic acid (3b, C21H32 03); treatment of this compound with chromic acid/pyridine complex rendered the aldehyde (4).
Subject(s)
Organometallic Compounds/chemistry , Asteraceae/chemistry , Diterpenes/chemistry , Esters/chemistry , Isomerism , Magnetic Resonance Spectroscopy , Oxidation-Reduction , Plant Leaves/chemistryABSTRACT
Hyptis colombiana is an aromatic shrub native to the Colombian and Venezuelan Andes. Aerial parts were collected in Mérida State at about 3100 m above sea level in February 2005, and May and October 2006. The essential oil was found to contain germacrene D and ß-caryophyllene as main constituents (about 50%). The February 2005 and October 2006 oils were found to have antibacterial activity against Staphylococcus aureus, but not the May 2006 oil, probably due to the lack of some minor constituent.
Subject(s)
Anti-Bacterial Agents/pharmacology , Oils, Volatile/pharmacology , Plant Oils/pharmacology , Anti-Bacterial Agents/chemistry , Bacteria/drug effects , Hyptis , Oils, Volatile/chemistry , Plant Components, Aerial , Plant Oils/chemistry , VenezuelaABSTRACT
The essential oil from the leaves ofRuilopezia bracteosa was obtained by hydrodistillation, and analyzed by GC-MS. Eighteen components, which made up 99.6% of the oil were identified, the most abundant being ß-myrcene (34.2%), α-pinene (24.3%), 7-epi-α-selinene (9.1%), ß-pinene (8.5%) and 6,9-guaiadiene (4.4%). Antibacterial activity was tested against Gram-positive and Gram-negative bacteria using broth microdilution and disk agar diffusion methods. MIC values found presented significant differences between both methods, which may be due to diffusion factors.
Subject(s)
Anti-Bacterial Agents/pharmacology , Asteraceae/chemistry , Oils, Volatile/pharmacology , Plant Oils/pharmacology , Anti-Bacterial Agents/chemistry , Bacteria/drug effects , Oils, Volatile/chemistry , Plant Leaves/chemistry , Plant Oils/chemistryABSTRACT
The essential oil of the leaves of Espeletia nana Cuatrec., obtained by hydrodistillation, was analyzed by GC-MS, which allowed the identification of 24 components, which made up 99.9% of the oil. The most abundant compounds were a-pinene (38.1%), beta-pinene (17.2%), myrcene (15.0%), spathulenol (4.2%), bicyclogermacrene (4.0%), a-zingiberene (4.0%), and gamma-himachalene (3.7%). Antibacterial activity was tested against Gram-positive and Gram-negative bacteria using the agar disk diffusion method. Activity was observed only against Gram-positive bacteria. MIC values were determined for Staphylococcus aureus ATCC 25923 (200 microg/mL) and Enterococcusfaecalis ATCC 29212 (600 microg/mL).
Subject(s)
Anti-Bacterial Agents/pharmacology , Asteraceae/chemistry , Oils, Volatile/analysis , Oils, Volatile/pharmacology , Gas Chromatography-Mass Spectrometry , Microbial Sensitivity TestsABSTRACT
Kaurenic acid (1a) is a tetracyclic diterpene that has an exocyclic double bond at delta16. Isokaurenic acid (2a) has an endocyclic delta15double bond. This compound has been isolated from Espeletia tenore (Espeletinae), a resinous plant from the Venezuelan Andes, but its occurrence is rare. In order to obtain a larger amount of 2a, the isomerization of la, which is easily obtained from other Espeletinae, was tried. Kaurenic acid methyl ester (1b) was treated with dil. HCl in CH3Cl/EtOH, after 6 h under reflux a yield of 41.5% isokaurenic acid methyl ester (2b) was obtained but 35.7% 16alpha-ethoxy-kauran-19-oic acid methyl ester (3b) had formed as a byproduct. Treating 1b with CF3COOH in refluxing CH2Cl2 permitted to obtain a yield of 66.6% of 2b in 4 h and only traces of 16alpha-hydroxy-kauran-19-oic acid methyl ester (3a) as a byproduct. Both isomers were separated on a silica gel column impregnated with 20% AgNO3. Treating 2b with KOH in refluxing DMSO yielded pure isokaurenic acid, no back isomerization was observed.
Subject(s)
Diterpenes/chemistry , Asteraceae/chemistry , Isomerism , Magnetic Resonance Spectroscopy , Mass Spectrometry , Spectrophotometry, Infrared , Trifluoroacetic Acid/chemistryABSTRACT
The bark of Bursera tomentosa was collected at full flowering stage in September 2002 at Cabudare, Lara State. The essential oil was isolated by hydrodistillation and it was analyzed by GC and GC/MS. Twenty eight components were identified which made up 90.1 percent of the oil. The main constituents of the essential oil were: spatulenol (11.4 percent, globulol (8.9 percent), epi alpha Cadinol (8.8 percent) and cis-ocimene (7.3 percent).
La corteza de Bursera tomentosa, fue recolectada en estado de floración en el mes de septiembre 2002 en Cabudare, Estado Lara. El aceite esencial fue obtenido por hidrodestilación y analizado por CG y CG/EM. Se identificó veinte y ocho compuestos que constituyen el 90.1por ciento del aceite. Los constituyentes mayoritarios del aceite esencial fueron spatulenol (11.4 por ciento), globulol (8.9 por ciento), epi-alfa-cadinol (8.8 por ciento) y cis-ocimeno (7.3 por ciento).
Subject(s)
Plant Oils/chemistry , Oils, Volatile/chemistry , Bursera/chemistry , Sesquiterpenes/analysis , Gas Chromatography-Mass SpectrometryABSTRACT
The hydrodistilled oil from the fruits of Bursera tomentosa, obtained in 0.2% yield, was analyzed by GC-MS. Nine components were identified, which made up 99.3% of the oil. The most abundant constituents were cis-ocimene (47.6%), n-nonane (28.2%) and germacrene-D (11.1%). The oil showed antibacterial activity against Staphylococcus aureus (ATCC 25923), Enterococcus faecalis (ATCC 29212) and Salmonella typhi (CDC 57), with MIC values of 80 microg/mL, 120 microg/mL and 100 microg/mL, respectively.