Crystal structure of 4-(benzo[d]thia-zol-2-yl)-1,2-dimethyl-1H-pyrazol-3(2H)-one.

In the title compound, C12H11N3OS, the inter-planar angle between the pyrazole and benzo-thia-zole rings is 3.31 (7)°. In the three-dimensional mol-ecular packing, the carbonyl oxygen acts as acceptor to four C-H donors (with one H⋯O as short as 2.25 Å), while one methyl hydrogen is part of the three-centre system H⋯(S, O). A double layer structure parallel to (01) can be recognized as a subsection of the packing.

Crystal structure of 2-{[5-(methyl-sulfan-yl)-4-phenyl-4H-1,2,4-triazol-3-yl]meth-yl}benzo[d]thia-zole.

In the structure of the title compound, C17H14N4O2, the triazole ring exhibits inter-planar angles of 63.86 (2) and 76.96 (2)° with the phenyl and benzo-thia-zole planes, respectively. The C-C-C angle at the methyl-ene group is rather wide at 114.28 (4)°. The packing involves three borderline C-H⋯N contacts, two of which combine to form layers parallel to ac, and a pairing of the triazole rings across an inversion centre [inter-planar distance of 3.1852 (2) Å].

Synthesis, Physicochemical Properties and Molecular Docking of New Benzothiazole Derivatives as Antimicrobial Agents Targeting DHPS Enzyme.

The drug-resistance problem is widely spread and becoming more common in community-acquired and nosocomial strains of bacteria. Therefore, finding new antimicrobial agents remains an important drug target. From this perspective, new derivatives of benzothiazole were synthesized and evaluated for their antimicrobial activity and ability to inhibit the DHPS enzyme. The synthesis was carried out by the reaction of benzothiazole N-arylsulphonylhydrazone with N-aryl-2-cyano-3-(dimethylamino)acrylamide, N-aryl-3-(dimethylamino)prop-2-en-1-one, arylaldehydes or diazonium salt of arylamine derivatives, which led to the formation of N-arylsulfonylpyridones 6a-d (yield 60-70%) and 12a-c (yield 50-60%),N-(2-(benzo[d]thiazole-2-yl)-3-arylacryloyl-4-methylsulfonohydrazide 14a-c (yield 60-65%), 4-(benzo[d]thiazole-2-yl)-5-aryl-1H-pyrazol-3(2H)-one 16a-c (yield 65-75%), and N'-(2-(benzo[d]thiazol-2-yl)-2-(2-arylhydrazono)acetyl)-4-arylsulfonohydrazide 19a-e (yield 85-70%). The antimicrobial evaluations resulted into a variety of microbial activities against the tested strains. Most compounds showed antimicrobial activity against S. aureus with an MIC range of 0.025 to 2.609 mM. The most active compound, 16c, exhibited superior activity against the S. aureus strain with an of MIC 0.025 mM among all tested compounds, outperforming both standard drugs ampicillin and sulfadiazine. The physicochemical-pharmacokinetic properties of the synthesized compounds were studied, and it was discovered that some compounds do not violate rule of five and have good bioavailability and drug-likeness scores. The five antimicrobial potent compounds with good physicochemical-pharmacokinetic properties were then examined for their inhibition of DHPS enzyme. According to the finding, three compounds, 16a-c, had IC50 values comparable to the standard drug and revealed that compound 16b was the most active compound with an IC50 value of 7.85 µg/mL, which is comparable to that of sulfadiazine (standard drug) with an IC50 value of 7.13 µg/mL. A docking study was performed to better understand the interaction of potent compounds with the binding sites of the DHPS enzyme, which revealed that compounds 16a-c are linked by two arene-H interactions with Lys220 within the PABA pocket.

Novel Synthesis and Antiviral Evaluation of New Benzothiazole-Bearing N-Sulfonamide 2-Pyridone Derivatives as USP7 Enzyme Inhibitors.

In this article, a series of benzothiazole-bearing N-sulfonamide 2-pyridone derivatives were synthesized via the reaction of benzothiazole sulfonylhydrazide with sodium salts of both (hydroxymethylene) cycloalkanones and unsaturated ketones, as well as ethoxymethylene derivatives. The structures of the resultant compounds were confirmed using IR, 1H NMR, 13C NMR, 1H-1H correlation spectroscopy (COSY), 1H-13C heteronuclear multiple bond coherence (HMBC), and 1H-13C heteronuclear multiple quantum coherence (HSQC) spectral analysis and elemental analysis. The newly synthesized compounds were evaluated in vitro for their antiviral activities against the HSV-1, HAV HM175, HCVcc genotype 4, CBV4, and HAdV7 viruses. Additionally, the compounds were examined for their cytotoxic effect on five normal cell lines. It was observed that five compounds were found to possess viral reduction of 50% or more against CBV4 with significant IC50, CC50, and SI values. In the case of HSV-1 and HAV HM175 viruses, three compounds have shown more than 50% reduction, while in the case of HCVcc genotype 4 and HAdV7 viruses, only two compounds demonstrated more than 50% reduction. Furthermore, the physicochemical properties of the most active compounds were evaluated. The two most potent compounds against HSV-1 virus, 7e and 13a, were evaluated for their inhibitory activity against USP7. Docking studies using Molecular Operating Environment (MOE) were used to identify the interactions between 7e and 13a compounds and the active site of the USP7 enzyme.