Synthesis of N-(6-Arylbenzo[d]thiazole-2-acetamide Derivatives and Their Biological Activities: An Experimental and Computational Approach.

A new series of N-(6-arylbenzo[d]thiazol-2-yl)acetamides were synthesized by C-C coupling methodology in the presence of Pd(0) using various aryl boronic pinacol ester/acids. The newly synthesized compounds were evaluated for various biological activities like antioxidant, haemolytic, antibacterial and urease inhibition. In bioassays these compounds were found to have moderate to good activities. Among the tested biological activities screened these compounds displayed the most significant activity for urease inhibition. In urease inhibition, all compounds were found more active than the standard used. The compound N-(6-(p-tolyl)benzo[d]thiazol-2-yl)acetamide was found to be the most active. To understand this urease inhibition, molecular docking studies were performed. The in silico studies showed that these acetamide derivatives bind to the non-metallic active site of the urease enzyme. Structure-activity studies revealed that H-bonding of compounds with the enzyme is important for its inhibition.

Synthesis, Density Functional Theory (DFT), Urease Inhibition and Antimicrobial Activities of 5-Aryl Thiophenes Bearing Sulphonylacetamide Moieties.

A variety of novel 5-aryl thiophenes 4a-g containing sulphonylacetamide (sulfacetamide) groups were synthesized in appreciable yields via Pd[0] Suzuki cross coupling reactions. The structures of these newly synthesized compounds were determined using spectral data and elemental analysis. Density functional theory (DFT) studies were performed using the B3LYP/6-31G (d, p) basis set to gain insight into their structural properties. Frontier molecular orbital (FMOs) analysis of all compounds 4a-g was computed at the same level of theory to get an idea about their kinetic stability. The molecular electrostatic potential (MEP) mapping over the entire stabilized geometries of the molecules indicated the reactive sites. First hyperpolarizability analysis (nonlinear optical response) were simulated at the B3LYP/6-31G (d, p) level of theory as well. The compounds were further evaluated for their promising antibacterial and anti-urease activities. In this case, the antibacterial activities were estimated by the agar well diffusion method, whereas the anti-urease activities of these compounds were determined using the indophenol method by quantifying the evolved ammonia produced. The results revealed that all the sulfacetamide derivatives displayed antibacterial activity against Bacillus subtiles, Escherichia coli, Staphylococcus aureus, Shigella dysenteriae, Salmonella typhae, Pseudomonas aeruginosa at various concentrations. Furthermore, the compound 4g N-((5-(4-chlorophenyl)thiophen-2-yl)sulfonyl) acetamide showed excellent urease inhibition with percentage inhibition activity ~46.23 ± 0.11 at 15 µg/mL with IC50 17.1 µg/mL. Moreover, some other compounds 4a-f also exhibited very good inhibition against urease enzyme.

A convenient method for the synthesis of (prop-2-ynyloxy)benzene derivatives via reaction with propargyl bromide, their optimization, scope and biological evaluation.

A highly convenient method has been developed for the synthesis of (prop-2-ynyloxy) benzene and its derivatives. Differently substituted phenol and aniline derivatives were allowed to react with propargyl bromide in the presence of K2CO3 base and acetone as solvent. The compounds were synthesized in good yields (53-85%). Low cost, high yields and easy availability of compounds helped in the synthesis. Electron withdrawing groups favor the formation of stable phenoxide ion thus in turn favors the formation of product while electron donating groups do not favor the reaction. Phenol derivatives gave good yields as compared to that of aniline. As aprotic polar solvents favor SN2 type reactions so acetone provided best solvation for the reactions. K2CO3 was proved to be good for the synthesis. Antibacterial, Antiurease and NO scavenging activity of synthesized compounds were also examined. 4-bromo-2-chloro-1-(prop-2-ynyloxy)benzene 2a was found most active compound against urease enzyme with a percentage inhibition of 82.00±0.09 at 100 µg/mL with IC50 value of 60.2. 2-bromo-4-methyl-1-(prop-2-ynyloxy)benzene 2d was found potent antibacterial against Bacillus subtillus showing excellent inhibitory action with percentage inhibition of 55.67±0.26 at 100 µg/ml wih IC50 value of 79.9. Based on results, it can be concluded that some of the synthesized compounds may have potential antiurease and antibacterial effects against several harmful substances.

Arylation and heteroarylation of thienylsulfonamides with organotrifluoroborates.

A mild, practical protocol has been developed for the Suzuki cross-coupling of unprotected thienylsulfonamides from air- and bench-stable organotrifluoroborates in the absence of a protecting group on the sulfonamide nitrogen. The developed synthetic method can be applied to the preparation of various arylated and heteroarylated thienylsulfonamides under conditions that are tolerant of a broad range of functional groups.

Efficient synthesis of 2-amino-6-arylbenzothiazoles via Pd(0) Suzuki cross coupling reactions: potent urease enzyme inhibition and nitric oxide scavenging activities of the products.

In general, benzothiazole derivatives have attracted great interest due to thier pharmaceutical and biological importance. New 2-amino-6-arylbenzothiazoles were synthesized in moderate to excellent yields via Suzuki cross coupling reactions using various aryl boronic acids and aryl boronic acid pinacol esters and the antiurease and nitric oxide (NO) scavenging activity of the products were also examined. The most active compound concerning urease enzyme inhibition was 6-phenylbenzo[d]thiazole-2-amine 3e, with an IC50 value of 26.35 µg/mL. Compound 3c, 6-(4-methoxyphenyl) benzo[d]thiazole-2-amine, exhibited the highest nitric oxide percentage scavenging at 100 µg/mL.

In vivo and ex vivo phagocytic potential of macrophages from progeny of breeder hens kept on ochratoxin A (OTA)-contaminated diet.

This study aimed to investigate the phagocytic potential of macrophages in progeny of breeder hens kept on an OTA-contaminated diet. For this purpose, 84 White Leghorn (WL) layer breeder hens (40-weeks-of-age) were divided into seven groups (A-G). Hens in Group A were fed a commercial layer ration while those in Groups B-G were kept on a diet amended with 0.1, 0.5, 1.0, 3.0, 5.0, or 10.0 mg OTA/kg, respectively, for up to 3 weeks (n = 12/treatment group; n = 4/time sub-group/treatment group). Fertile eggs were set for hatching on a weekly basis to get the progeny of each week separately. Hatched chicks (n = 10 from each group) were injected with India ink at day 14-of-age to study the in vivo phagocytosis of carbon particles. At day 30, abdominal macrophages were collected from 15 chicks/group and were used to assess their ex vivo/in vitro phagocytic potential against sheep red blood cells (SRBC) as well as for nitrite production upon challenge with lipopolysaccharide (LPS). The phagocytic indices of the reticuloendothelial system of all three sets of progeny (chicks obtained from hens fed OTA for 7, 14, and 21 days) were significantly lower than values seen with Group A chicks. The number of macrophages that were actively phagocytic, the number of SRBC internalized per macrophage, and the extent of nitrite production after stimulation with LPS were each significantly lower in the cells obtained from chicks of breeder hens that had been maintained on the OTA-contaminated diets. The findings of this study clearly showed that there are immunosuppressive effects-in terms of depressed in vivo and in vitro macrophage functionality-in progeny of OTA-fed breeder hens.

Immunological responses of male White Leghorn chicks kept on ochratoxin A (OTA)-contaminated feed.

This study was designed to evaluate some immunological responses of male White Leghorn (WL) chicks kept on an ochratoxin A (OTA)-contaminated diet. For this purpose, 350 1-day-old male WL chicks were divided into five groups (A-E). Group A was kept as control, while Groups B, C, D, and E were fed OTA-contaminated feed at 0.1, 0.5, 1.0, and 1.5 mg/Kg diet, respectively, for 21 days, and then basal ration for the remaining period. At 14- and 16-days of age, random chicks (n = 10) from each group were used for analyses of phagocytic function of the reticuloendothelial system or for measuring the lymphoproliferative responses to intradermally-administered T-cell mitogen, phytohemagglutinin-P (PHA-P), respectively. At 30-days of age, abdominal macrophages were collected from 15 chicks/group and utilized for determination of their phagocytic potential and for nitrite production. Antibody (Ab) titers (i.e., total antibodies, IgM, and IgG) against sheep red blood cells (SRBC) were determined at 7 and 14 days after a primary (at 7 days of age) and a booster (given 14 days after primary [at 21-days of age]) dose (intravenous) of the antigen. Data from the present study showed that the relative weight of the bursa of Fabricius of chicks fed OTA for 14 and 21 days and the spleen of chicks fed OTA for 21 days were significantly lower than their control counterpart. Phagocytic function of reticuloendothelial system evaluated by carbon clearance, and lymphoproliferative response to PHA-P, of chicks kept on OTA-contaminated diet were significantly lowered. The percentage of abdominal macrophages displaying phagocytosis of SRBC, the number of SRBC/macrophage, and nitrite production were each significantly lower in cells from chicks in the OTA-fed groups. Total Ab (at days 7 and 14 post-booster SRBC injection) and IgG (at day 14 post-primary and day 7 post-booster SRBC injection) titers against SRBC showed significant reductions in the groups fed OTA-contaminated diet. The findings of this study are in line with the previous work suggesting the immunosuppressive effect of OTA in male WL chicks regarding functional impairment in some of the components of the immune system.