ABSTRACT
BACKGROUND: Marine actinomycetes are among indispensable sources of natural bioactive compounds with unique antimicrobial and anti-cancer activities. OBJECTIVE: Herein, it was aimed to elucidate the bioactive potential of a marine-derived Streptomyces ovatisporus S4702T, isolated previously. METHODS: Streptomyces ovatisporus S4702T was cultured in N-Z Amine broth, and extraction was carried out using different organic solvents. Bioassay-guided purification was followed by chemical characterization using NMR and LC-MS/MS. The compound was then evaluated for its antibacterial, antioxidant and cytotoxic activities. RESULTS: Etyl acetate extracts gave the highest antibacterial activity, and chemical characterization of this extract indicated the formula as C15H29O5N3 and the corresponding possible molecular structure as 4H-chromen-4-one derivative. It was found highly potent against Bacillus subtilis ATCC 6633 (MIC: 0.25 µg ml-1) and Micrococcus luteus ATCC 9341 (MBC: 0.5 µg ml-1). It has no remarkable antioxidant activity, but a higher EC50 value and less cytotoxicity against normal cells. The EC50 values of this chromen derivative were found as 9.68 µg ml-1 for human colon carcinoma, 9.93 µg ml-1 for human prostate adenocarcinoma and 25.5 µg ml-1 for human embryonic kidney cells. CONCLUSION: Overall, the presented 4H-chromen-4-one derivative is a remarkable bioactive compound with potent antibacterial and cytotoxic activity. With its high bioactive potential, it is proposed as a good candidate in medicine.
Subject(s)
Anti-Bacterial Agents/pharmacology , Antineoplastic Agents/pharmacology , Antioxidants/pharmacology , Chromones/pharmacology , Streptomyces/chemistry , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/isolation & purification , Antineoplastic Agents/chemistry , Antineoplastic Agents/isolation & purification , Antioxidants/chemistry , Antioxidants/isolation & purification , Apoptosis/drug effects , Benzothiazoles/antagonists & inhibitors , Cell Proliferation/drug effects , Cell Survival/drug effects , Cells, Cultured , Chromones/chemistry , Chromones/isolation & purification , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , Gram-Negative Bacteria/drug effects , Gram-Positive Bacteria/drug effects , Humans , Microbial Sensitivity Tests , Molecular Structure , Phenethylamines/antagonists & inhibitors , Structure-Activity Relationship , Sulfonic Acids/antagonists & inhibitorsABSTRACT
BACKGROUND: Indole-based heterocyclic compounds play important roles in pharmaceutical chemistry due to their unexpected biological and pharmacological properties. OBJECTIVE: Herein, we describe novel biological properties (antioxidant, antimicrobial and anti-cancer) of 3- bromo-1-ethyl-1H-indole (BEI) structure. METHODS: BEI was synthesized from 1-Methyl-2-phenylindole and N-bromosuccinimide and was characterized by using 1H and 13C NMR. Cytotoxicity was determined by MTT assay. Apoptosis analysis of BEI was determined by Arthur™ image-based Cytometer. Different methods were applied to assess the antioxidant activity of BEI. Molecular docking studies were conducted to determine the interactions of bonding between GST isozymes and BEI. RESULTS: According to the antioxidant and antimicrobial activity assays, BEI compound showed reduced total antioxidant activity compared to the Trolox standard, whereas it showed moderate antimicrobial activity against Aspergillus niger and Phytophora eryhtrospora. Notably, the BEI compound demonstrated substantial selective cytotoxicity for the first time towards cancer cell lines, and there existed a significant decrease in the percentage of live cells treated with BEI, in comparison to the control ones. Interestingly, BEI exhibited a promising glutathione S-transferase isozymes inhibition. CONCLUSION: The results of this study suggest that BEI seems to be a promising molecule to be used in the design of new anti-cancer agents that provide superiority to present commercial anti-cancer drugs.
Subject(s)
Anti-Bacterial Agents/pharmacology , Antifungal Agents/pharmacology , Antineoplastic Agents/pharmacology , Antioxidants/pharmacology , Enzyme Inhibitors/pharmacology , Glutathione Transferase/antagonists & inhibitors , Anti-Bacterial Agents/chemical synthesis , Anti-Bacterial Agents/chemistry , Antifungal Agents/chemical synthesis , Antifungal Agents/chemistry , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Antioxidants/chemical synthesis , Antioxidants/chemistry , Apoptosis/drug effects , Bacteria/drug effects , Benzothiazoles/antagonists & inhibitors , Biphenyl Compounds/antagonists & inhibitors , Cell Proliferation/drug effects , Cell Survival/drug effects , Cells, Cultured , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , Enzyme Inhibitors/chemical synthesis , Enzyme Inhibitors/chemistry , Fungi/drug effects , Glutathione Transferase/metabolism , Humans , Isoenzymes/antagonists & inhibitors , Isoenzymes/metabolism , Microbial Sensitivity Tests , Molecular Structure , Picrates/antagonists & inhibitors , Structure-Activity Relationship , Sulfonic Acids/antagonists & inhibitorsABSTRACT
Helicoverpa armigera is an insect that causes important economic losses in crops. To reduce this loss, pyrethroids have been commonly used against H. armigera in farming areas. However, excess and continuous usage of pyrethroids cause resistance in H. armigera. Therefore, expressions of midgut proteins of two H. armigera field populations were compared to those of a susceptible strain by 2-D PAGE and MALDI-ToF-MS. Our results indicate that H. armigera reacts to pyrethroid-induced stress mainly by increasing the expression of energy metabolism-related proteins, such as ATP synthase and arginine kinase. NADPH cytochrome P450 reductase, also up-regulated, could play a role in detoxification of toxic pyrethroid metabolites, such as 3-phenoxybenzaldehyde. Interestingly, while GSTs were not found up-regulated in the comparative proteome analysis, biochemical assays showed significant increases of enzyme activities in both field populations as compared to the susceptible strain. Similarly, although esterases were not found differentially expressed, biochemical assays showed significant increases of esterase activities in both field populations. Thus, esterases are also proposed to be involved in metabolic responses towards pyrethroid insecticide-induced stress. In conclusion, we suggest increased energy metabolism in the midgut tissue of H. armigera as a general prerequisite for compensating the costs of energy-consuming detoxification processes.