ABSTRACT
In this study, the N,N,O metal chelator 2-pyridinecarboxaldehydeisonicotinoyl hydrazone (HPCIH, 1) and its derivatives 2-acetylpyridine-(HAPIH 2), 2-pyridineformamide-(HPAmIH, 3) and pyrazineformamide-(HPzAmIH, 4) were employed in the synthesis of four copper(II) complexes, [Cu(HPCIH)Cl2]·0.4H2O (5), [Cu(HAPIH)Cl2]·1.25H2O (6), [Cu(HPAmIH)Cl2]·H2O (7) and [Cu(HPzAmIH)Cl2]·1.25H2O (8). The compounds were assayed for their action toward Mycobacterium tuberculosis H37Rv ATCC 27294 strain and the human tumor cell lines OVCAR-8 (ovarian cancer), SF-295 (glioblastoma multiforme) and HCT-116 (colon adenocarcinoma). All copper(II) complexes were more effective in reducing growth of HCT-116 and SF-295 cells than the respective free hydrazones at 5 µg/mL, whereas only complex 7 was more cytotoxic toward OVCAR-8 lines than its ligand HPAmIH. 6 proved to be cytotoxic at submicromolar doses, whose IC50 values (0.39-0.86 µM) are similar to those ones found for doxorubicin (0.23-0.43 µM). Complexes 5 and 6 displayed high activity against M. tuberculosis (MIC = 0.85 and 1.58 µM, respectively), as compared with isoniazid (MIC = 2.27 µM), which suggests the compounds are attractive candidates as antitubercular drugs.
Subject(s)
Antineoplastic Agents/pharmacology , Antitubercular Agents/pharmacology , Coordination Complexes/chemistry , Coordination Complexes/pharmacology , Isoniazid/chemistry , Antineoplastic Agents/chemistry , Antitubercular Agents/chemistry , Cell Line, Tumor , Coordination Complexes/chemical synthesis , Drug Evaluation, Preclinical/methods , HCT116 Cells , Humans , Hydrazones/chemistry , Microbial Sensitivity Tests , Molecular Structure , Mycobacterium tuberculosis/drug effects , Spectrophotometry, InfraredABSTRACT
New oxirane derivatives were synthesized using six naphthoquinones as the starting materials. Our biological results showed that these oxiranes acted as trypanocidal agents against Trypanosoma cruzi with minimal cytotoxicity in the VERO cell line compared to naphthoquinones. In particular, oxirane derivative 14 showed low cytotoxicity in a mammalian cell line and exhibited better activity against epimastigote forms of T.cruzi than the current drug used to treat Chagas disease, benznidazole.
Subject(s)
Ethylene Oxide/pharmacology , Naphthoquinones/chemistry , Naphthoquinones/pharmacology , Trypanocidal Agents/chemistry , Trypanocidal Agents/pharmacology , Trypanosoma cruzi/drug effects , Animals , Cell Death/drug effects , Cell Survival/drug effects , Chlorocebus aethiops , Dose-Response Relationship, Drug , Drug Evaluation, Preclinical , Ethylene Oxide/analogs & derivatives , Ethylene Oxide/chemistry , Models, Molecular , Molecular Structure , Parasitic Sensitivity Tests , Structure-Activity Relationship , Trypanocidal Agents/chemical synthesis , Trypanosoma cruzi/cytology , Trypanosoma cruzi/growth & development , Vero CellsABSTRACT
Concern about nitrite in processed meats has increased consumer demand for natural products manufactured without nitrite or nitrate. Studies on commercial meat products labeled as "Uncured" and "No-Nitrite-or-Nitrate-Added" have shown less control of nitrite in these products and greater potential growth of bacterial pathogens. To improve the safety of the "naturally cured" meats, several natural ingredients were studied in a cured cooked meat model system (80:20 pork, 10% water, 2% salt, and 150 or 50 ppm ingoing sodium nitrite) that closely resembled commercial frankfurters to determine their inhibitory effect on Listeria monocytogenes. Results showed that cranberry powder at 1%, 2% and 3% resulted in 2-4 log cfu/g less growth of L. monocytogenes compared to the control with nitrite alone (P<0.05). Other natural compounds, such as cherry powder, lime powder and grape seed extract, also provided measureable inhibition to L. monocytogenes when combined with cranberry powder (P<0.05).
Subject(s)
Anti-Infective Agents/pharmacology , Biological Products/pharmacology , Fast Foods/microbiology , Food Microbiology , Food Preservatives/pharmacology , Listeria monocytogenes/drug effects , Meat Products/microbiology , Animals , Colony Count, Microbial , Fast Foods/analysis , Fermentation , Fruit/chemistry , Listeria monocytogenes/growth & development , Listeria monocytogenes/isolation & purification , Meat Products/analysis , Nitrites/analysis , Plant Extracts/pharmacology , Powders , Prunus/chemistry , Sodium Nitrite/pharmacology , Sus scrofa , Time Factors , Vaccinium macrocarpon/chemistryABSTRACT
Activation of either the alternative or classical pathway of complement generated a factor which induced release of histamine from both non-allergic and allergic human basophils. This factor probably is derived from the complement system since 1) its formation was associated with loss of C3 activity in human serum, 2) chemotactic factor, probably also a complement product, was generated simultaneously, 3) heat inactivation blocked its formation, 4) anti-C3 and anti-C5 blocked formation of the factor, and finally 5) anti-C5 inhibited the activity of the factor once it had been formed. It appears that both complement-mediated and allergen-mediated release of histamine from basophils are secretory, non-cytolytic pathways since both were maximal at 37 degrees C, required the presence of divalent cations, and were inhibited by theophylline. One consistent difference between these two mechanisms was noted: complement-initiated release of histamine occurred more quickly.