Synthesis, antimicrobial activity and molecular docking studies of spiroquinoline-indoline-dione and spiropyrazolo-indoline-dione derivatives.

Spiro[benzo[h]quinoline-7,3'-indoline]diones and spiro[indoline-3,4'-pyrazolo[3,4-b]quinoline]diones were efficiently synthesized via one-pot multi-component reactions under ultrasound-promoted conditions. Spiro[benzo[h]quinoline-7,3'-indoline]dione derivatives were successfully developed by the reaction of isatins, naphthalene-1-amine and 1,3-dicarbonyl compounds. The spiro[indoline-3,4'-pyrazolo[3,4-b]quinoline]dione derivatives were prepared by the reaction of isatins, 5-amino-1-methyl-3-pheylpyrazole, and 1,3-dicarbonyl compounds by using ( ±)-camphor-10-sulfonic acid as a catalyst in H2O/EtOH (3:1 v/v) solvent mixture. The antibacterial activity of the synthesized compounds was evaluated against, Enterococcus faecalis, Staphylococcus aureus and Candida albicans. Compounds 4b, 4h, and 6h showed the strongest antimicrobial activity toward both bacteria. The MIC values of these compounds ranged from 375-3000 µg/mL. The effect of these compounds (4b, 4h, 6h) as a function of applied dose and time was investigated by a kinetic study, and the interaction with these antimicrobial results was simulated by a molecular docking study. We also used the docking approach with Covid-19 since secondary bacterial infections. Docking showed that indoline-quinoline hybrid compounds 4b and 4h exerted the strongest docking binding value against the active sites of 6LU7. In addition, the synthesized compounds had a moderate to good free radical scavenging activity.

Synthesis, Structural Investigation, Hirshfeld Surface Analysis, and Biological Evaluation of N-(3-Cyanothiophen-2-yl)-2-(thiophen-2-yl)acetamide.

In this study, a novel heterocyclic amide derivative, N-(3-cyanothiophen-2-yl)-2-(thiophen-2-yl)acetamide (I), was obtained by reacting 2-aminothiophene-3-carbonitrile with activated 2-(thiophen-2-yl)acetic acid in a N-acylation reaction and characterized by elemental analyses, FT-IR, 1H and 13C NMR spectroscopic studies, and single crystal X-ray crystallography. The crystal packing of I is stabilized by C-H···N and N-H···N hydrogen bonds. In addition, I was investigated computationally using the density functional theory (DFT) method with the B3LYP exchange and correlation functions in conjunction with the 6311++G(d,p) basis set in the gas phase. Fukui function (FF) analysis was also carried out. Electrophilicity-based charge transfer (ECT) method and charge transfer (ΔN) were computed to examine the interactions between I and DNA bases (such as guanine, thymine, adenine, and cytosine). The most important contributions to the Hirshfeld surface are H···H (21%), C···H (20%), S···H (19%), N···H (14%), and O···H (12%). An ABTS antioxidant assay was used to evaluate the in vitro antioxidant activity of I. The compound exhibited moderate antioxidant activity. The antimicrobial activity of the title molecule was investigated under aseptic conditions, using the microdilution method, against Gram-positive and Gram-negative bacterial strains, and it also demonstrated significant activity against yeasts (Candida glabrata ATCC 90030, Candida krusei ATCC 34135). The findings revealed that the molecule possesses significant antioxidant and antimicrobial properties.

Streptomyces boluensis sp. nov., isolated from lake sediment.

A novel Gram-stain positive, aerobic, non-motile actinobacterium, designated strain YC537T, was isolated from lake sediment collected from Yenicaga Lake, Bolu, Turkey, and subjected to a polyphasic taxonomic approach. The organism had phylogenetic, chemotaxonomic, cultural and morphological properties consistent with its classification in the genus Streptomyces. 16S rRNA gene sequence analysis of strain YC537T showed that it is closely related to the type strain of Streptomyces ziwulingensis F22T (97.9% sequence similarity), Streptomyces tauricus JCM 4837 T (97.7%) and Streptomyces beijiangensis NBRC 100044 T (97.6%). The cell wall of the strain contained LL-diaminopimelic acid and the cell-wall sugars were glucose, galactose and ribose. The major phospholipids of strain YC537T were diphosphatidylglycerol, phosphatidylethanolamine and phosphatidylinositol. The predominant menaquinones were identified as MK-9(H6) and MK-9(H8). The major cellular fatty acids were iso-C16:0, iso-C14:0, anteiso-C15:0 and iso-C15:0. Consequently, strain YC537T is considered to represent a novel species in the genus Streptomyces, for which the name Streptomyces boluensis sp. nov. is proposed. The type strain is YC537T (= KCTC 39750 T = DSM 102303 T).

Derivatives of pyridine and thiazole hybrid: Synthesis, DFT, biological evaluation via antimicrobial and DNA cleavage activity.

A novel series of the 2-pyridine substituted 3a-e and 4-pyridine substituted 4a-e thiazole derivatives were synthesized, characterized, and evaluated for the biological activity. Crystallographic parameters and inter- and intramolecular interactions of 3a and 3c single crystals were examined through XRD analysis. The chemical reactivity potentials of the compounds were evaluated, by comparing with a theoretical approach based on DFT. The biological activity properties of synthesized compounds were determined by antimicrobial activity with Gram positive, Gram negative, Yeast via minimal inhibitory concentration (MIC) method and DNA cleavage activity studies. The most obvious findings to emerge from this study are that on the basis of both biological activity and chemical reactivity 4-pyridine thiazole hybrid compounds 4a-e showed more potent activity than 3a-e. In general, the antimicrobial activity of synthesized compounds follows the Bacillus cereus > Staphylococcus aureus > Candida albicans > Escherichia coli > Pseudomonas aeruginosa. The most potent compound 4c (MIC values 0.02 mM) exhibited antimicrobial activity against Staphylococcus aureus and Bacillus cereus. Furthermore, this compound has a good electrophilicity index value (4.56 eV).

Streptomyces ureilyticus sp. nov. and Streptomyces mesophilus sp. nov., two novel Actinobacteria with antimicrobial activity isolated from lake sediment.

Two novel Actinobacteria, designated strains YC419T and YC504T, were isolated from a sediment sample collected from Lake Yeniçaga, Bolu Province, Turkey. Chemotaxonomic and morphological characteristics of isolates were found to be typical of members of the genus Streptomyces. Phylogenetic analyses based on 16S rRNA gene sequences revealed that strain YC419T was most closely related to Streptomyces vastus NBRC 13094T (99.0 %) and 'Streptomyces xiangluensis' NEAU-LA29 (98.6 %), and strain YC504T was to most closely related to Streptomyces caldifontis NCCP-1331T (98.6 %) and Streptomyces indicus IH32-1T (98.0 %). The cell walls of the two strains contained ll-diaminopimelic acid as the diagnostic diamino acid and the whole-cell hydrolysates were glucose, mannose and ribose. The predominant menaquinones were MK-9(H8) and MK-9(H6) in both strains. The major polar lipids of strain YC419T were diphosphatidylglycerol, phosphatidylethanolamine and phosphatidylinositol, while strain YC504T had a similar profile but lacking diphosphatidylglycerol. The G+C contents of the genomic DNAs were 69.6 and 70.3 mol% for strains YC419T and YC504T, respectively. The phenotypic and genotypic data indicated that these two strains were readily distinguished from one another and the type strains of the other species classified in the genus Streptomyces. Therefore, the strains are suggested to represent two novel species of the genus Streptomyces, for which the names Streptomyces ureilyticus sp. nov. and Streptomyces mesophilus sp. nov. are proposed. The type strains are YC419T (=DSM 102299T=KCTC 39757T) and YC504T (=DSM 102300T=KCTC 39756T), respectively.

The role of oxidative stress genes and effect of pH on methylene blue sensitized photooxidation of Escherichia coli.

In this study, the survival time of wild type E. coli W3110 and 11 mutants was analysed with a plate count method in methylene blue added or control groups under daylight fluoroscence illumination (4950 lux) at different pH values (5.0, 6.0, 7.0, and 8.0) in phosphate buffer. As a result, while the number of bacteria did not decrease under photooxidative stress at pH 5.0 and 6.0 during a 6-hour incubation, the wild type and all mutants decreased more than 2 log. at pH 8.0, and approximately one log. at pH 7.0. It was determined that a 2 log decrease in wild type E. coli takes 3.7 h according to t99 value at pH 8, these values were 2.39 h in the katE mutant, 2.64 h in the soxR mutant, 2.67 h in the oxyR mutant, 2.71 h in the sodB mutant, 3 h in the btuE mutant, 3.38 h in the zwf mutant and 3.40 h in the soxS mutant, respectively (p < 0.05). The roles of these genes were proved with complement tests. Finally, it is found that the effectiveness of photooxidative stress is in direct relation with pH, and the katE, soxR, oxyR, sodB, btuE, zwf, and soxS genes are important for the protection against this stress.

Escherichia coli: dominance of red light over other visible light sources in establishing viable but nonculturable state.

In this study, the effect of UV-A and different wavelengths of visible light irradiations combined with or without a photosensitizer (methylene blue, MB) on the establishment of viable but nonculturable (VBNC) state in Escherichia coli was investigated. Survival of the E. coli was investigated by measuring plate counts, respiring cell count (RCC), direct viable count (DVC) and total counts over a period of up to 72 h. The inhibition rates of various light sources in the presence or absence of MB on E. coli in seawater were ranked in the order UV-A>red light>white light>blue light>green light (from greatest to least activation). E. coli survived for 10.2, 19.0, 21.3 and 24.04 h under exposure to red, white, blue and green light and for 6.8 h under exposure to UV-A in the presence of MB according to t(99). Although the VC declined to undetectable levels in a relatively short time, the RCC showed that some cells were still capable of respiration and, therefore, are assumed to have entered the VBNC phase. This is the first time that red light has been shown to have a stronger effect on E. coli survival and VBNC than white, green and blue light in seawater environment.

Viable but non-culturable state (VBNC) of Escherichia coli related to EnvZ under the effect of pH, starvation and osmotic stress in sea water.

When exposed extreme environmental conditions such as sea water, bacteria have been shown different survival strategy for continue their life. One of this strategy known as viable but nonculturable (VBNC) state which is very important for nondifferiation bacteria. VBNC cells cause serious human health problems. Little is known, however, about the genetic mechanisms underlying the VBNC state. Under different environmental conditions, porins are important in the survival strategy of bacteria. EnvZ/OmpR work together as regulators of ompF and ompC gene expression. It is known that the EnvZ system has a role in VBNC state. In this study we tried to find out the viability of EnvZ, OmpC and OmpF mutant E. coli under stress effect of osmolarity, pH and starvation. Bacteria were suspended in filtered-autoclaved sea water microcosms and numbers determined over 25 day incubation periods by plate count (PC), direct viable count (DVC) and count of cells capable of respiration (RCC). As regard to results, alkaline pH affected E. coli more than acidic pH, which led to decline in number. On the contrary glycine betaine addition to sea water protected E. coli porin mutants and also reduced the death rate of bacteria. Under the effect of pH, osmotic stress and starvation stress, wild type E. coli and porin mutants entered a dormant state or became VBNC with the exception of MSZ31 (envZ mutant) E. coli cells which did not enter the VBNC state under the three tested stress conditions. This study is the first report to demonstrate that E. coli could not enter the VBNC state in the lack of EnvZ product under the stress of osmolarity, pH and starvation and the relationship between EnvZ and VBNC state are not affected by pH, osmolarity and starvation.