Discovery of potent carbonic anhydrase,acetylcholinesterase, and butyrylcholinesterase enzymes inhibitors: The new amides and thiazolidine‐4‐ones synthesized on an acetophenone base

Compounds containing nitrogen and sulfur atoms can be widely used in various fields, including industry, medicine, biotechnology, and chemical technology. Among them, amides of acids and heterocyclic compounds have an important place. These amides and thiazolidine‐4‐ones showed good inhibitory action against butyrylcholinesterase (BChE), acetylcholinesterase (AChE), and human carbonic anhydrase isoforms. AChE exists at high concentrations in the brain and red blood cells. BChE is an important enzyme that is plentiful in the liver, and it is released into the blood in a soluble form. They were demonstrated to have effective inhibition profiles with K_i values of 23.76–102.75 nM against hCA I, 58.92–136.64 nM against hCA II, 1.40–12.86 nM against AChE, and 9.82–52.77 nM against BChE. On the other hand, acetazolamide showed K_i value of 482.63 ± 56.20 nM against hCA I, and 1019.60 ± 163.70 nM against hCA II. Additionally, Tacrine inhibited AChE and BChE, showing K_i values of 397.03 ± 31.66 and 210.21 ± 15.98 nM, respectively.     

Experimental and molecular docking investigation on DNA interaction of N‐substituted phthalimides: antibacterial,antioxidant and hemolytic activities

A series of Schiff base molecules derived from a phthalimide scaffold was investigated as efficient antibacterial, antioxidant and DNA‐interacting agents. The spectroscopic characterization of these derivatives was studied in detail using elemental analysis and spectroscopic techniques. The DNA‐binding profile of title molecules against Ct‐DNA (calf thymus) was investigated by absorbance, fluorescence, hydrodynamics and thermal denaturation investigations. The bacterial inhibition potential of these molecules was investigated against Escherichia coli and Staphylococcus aureus. Molecule 3c emerged as the most active against S. aureus (IC₅₀: 14.8 μg/mL), whereas compounds 3a and 3b displayed potential antibacterial activities against E. coli (IC₅₀: 49.7 and 67.6 μg/mL). Molecular docking studies of these compounds against GlcN‐6‐P synthase were carried out to rationalize antibacterial efficiency of these molecules. These newly synthesized molecules were screened for their scavenging capacity against 2,2‐diphenyl‐1‐picryl‐hydrazyl (DPPH) and H₂O₂ free radicals and the results were compared with ascorbic acid as synthetic antioxidant. The title molecules 3a, 3b and 3e showed less than 20% hemolysis, which indicated their significant non‐toxic behavior.     

Cytogenetic study on Microtus guentheri (Danford and Alston, 1880) (mammalia: rodentia) from Turkey: constitutive heterochromatin distribution and nucleolar organizer regions

Conventionally stained, C- and Ag-NOR banded karyotypes of Guenther's vole, Microtus guentheri were studied from Turkey. The species possesses a karyotype of 2n = 54, NFa = 52 and NF = 54 in specimens from Kahramanmara? and Gaziantep provinces, whereas NF = 56 in females and NF = 55 in males were found in individuals from Kirikkale and Nev?ehir provinces. The X chromosome was a large acrocentric (NF = 54) or submetacentric (NF = 55, 56) while the Y chromosome was a small telocentric in all specimens examined. Blocks of constitutive heterochromatin were located in the pericentromeric areas of autosomes including the X chromosome. Nucleolar organizer regions (NORs) were located at the telomeric regions of the short arms of five acrocentric pairs and centromeric regions of two telocentric pairs in the Nev?ehir and Kirikkale specimens.     

One size fits all in prostate cancer: a story tale whose time has come and gone

The touchstone to evaluate accurately the aggressiveness and invasiveness of prostate cancer is something of a holy grail in the facet of urologic oncology. Gene expression and sequencing studies have improved our interpretations of the genetic determinants of the disease but are unsuccessful in the establishment of any unified classification to improve the molecular stratification. These questions addressing failure in rational drug design are difficult to answer in the multifaceted and heterogeneous pathogenesis of prostate cancer. In this review, we have developed a roadmap of the "recalcitrant prostate cancer proteome" to recognize the aspects of prostate cancer that may be helpful in effectively translating these findings to the clinic.     

Role of proline and glycinebetaine pretreatments in improving heat tolerance of sprouting sugarcane (<Emphasis Type="Italic">Saccharum</Emphasis> sp.) buds

High temperature strongly hampers the plant growth particularly at early growth stages. In this study, changes in some physiological and anatomical characteristics and possibility of mitigating the adversities of heat stress by soaking sugarcane nodal buds in 20 mM proline and glycinebetaine (GB) solutions have been explored. Heat stress reduced the rate of bud sprouting nonetheless soaking the setts in proline followed by GB was beneficial. In addition, heat stress reduced the bud fresh and dry weights, generated H₂O₂, reduced the tissue levels of K⁺ and Ca²⁺, while increased the osmolytes synthesis in a time course manner. Heat stress also delayed the emergence and expansion of new bud leaves, by restricting the number and area of mesophyll cells. It also caused poor and aberrant development and diffused appearance of mesophyll cells and vascular bundles in the bud leaves. However, soaking of buds in proline and GB solutions substantially reduced the H₂O₂ production, improved the accumulation of soluble sugars and protected the developing tissues from heat stress effects; although proline was more effective than GB. Correlations of various attributes indicated that soaking in GB and proline restricted the H₂O₂ generation, improved K⁺ and Ca²⁺ contents, and increased the concentrations of free proline, GB and soluble sugars eventually improving the heat tolerance of buds. Cost-benefit analysis showed that, considering increase in sprouting of buds, soaking in 20 mM solution of both osmoprotectants is economical.     

Proteomic identification of differentially expressed proteins in the anoxic rice coleoptile

Rice is the staple food for more than fifty percent of the world's population, and is therefore an important crop. However, its production is hindered by several biotic and abiotic stresses. Although rice is the only crop that can germinate even in the complete absence of oxygen (i.e. anoxia), flooding (low oxygen) is one of the major causes of reduced rice production. Rice germination under anoxia is characterized by the elongation of the coleoptile, but leaf growth is hampered. In this work, a comparative proteomic approach was used to detect and identify differentially expressed proteins in the anoxic rice coleoptile compared to the aerobic coleoptile. Thirty-one spots were successfully identified by MALDI-TOF MS analysis. The majority of the identified proteins were related to stress responses and redox metabolism. The expression levels of twenty-three proteins and their respective mRNAs were analyzed in a time course experiment.     

Tetra primer ARMS-PCR relates folate/homocysteine pathway genes and ACE gene polymorphism with coronary artery disease

Cardiovascular disorders and coronary artery disease (CAD) are significant contributors to morbidity and mortality in heart patients. As genes of the folate/homocysteine pathway have been linked with the vascular disease, we investigated association of these gene polymorphisms with CAD/myocardial infarction (MI) using the novel approach of tetraprimer ARMS-PCR. A total of 230 participants (129 MI cases, 101 normal subjects) were recruited. We genotyped rs1801133 and rs1801131 SNPs in 5'10' methylenetetrahydrofolate reductase (MTHFR), rs1805087 SNP in 5' methyltetrahydrofolate homocysteine methyltransferase (MTR), rs662 SNP in paroxanse1 (PON1), and rs5742905 polymorphism in cystathionine beta synthase (CBS). Angiotensin converting enzyme (ACE) insertion/deletion polymorphism was detected through conventional PCR. Covariates included blood pressure, fasting blood sugar, serum cholesterol, and creatinine concentrations. Our results showed allele frequencies at rs1801133, rs1801131, rs1805087 and the ACE insertion/deletion (I/D) polymorphism varied between cases and controls. Logistic regression, after adjusting for covariates, demonstrated significant associations of rs1801133 and rs1805087 with CAD in the additive, dominant, and genotype model. In contrast, ACE I/D polymorphism was significantly related with CAD where recessive model was applied. Gene-gene interaction against the disease status revealed two polymorphism groups: rs1801133, rs662, and rs1805087; and rs1801131, rs662, and ACE I/D. Only the latter interaction maintained significance after adjusted for covariates. Our study concludes that folate pathway variants exert contributory influence on susceptibility to CAD. We further suggest that tetraprimer ARMS-PCR successfully resolves the genotypes in selected samples and might prove to be a superior technique compared to the conventional approach.