Facile synthesis of substituted 2-aroylbenzo[b]thiophen-3-ols to form novel triazole hybrids using click chemistry.

An efficient one-pot method is proposed for the synthesis of 2-aroylbenzo[b]thiophen-3-ols from 2-mercaptobenzoic acid and various substituted aryl bromomethyl ketones in the presence of triethylamine. The reaction is likely to proceed through SN2-type nucleophilic attack of the sulfhydryl group in thiosalicylic acid on bromomethyl ketone in the presence of a base to afford sulfanylbenzoic acid, which undergoes an intramolecular cyclization in situ to furnish 2-aroylbenzo[b]thiophen-3-ol in high yield. To investigate the utility of the synthesized benzothiophene scaffold, an alkyne moiety was introduced at the 3-hydroxy position and subsequently subjected to a click reaction to form novel benzothiophene-triazole hybrids in good yields. A simple and straightforward approach to synthesizing 2-aroylbenzo[b]thiophen-3-ols can open new avenues for discovering novel biological and pharmaceutical compounds.

Endophytic bacteria of Fagonia indica Burm. f revealed to harbour rich secondary antibacterial metabolites.

Endophytic bacteria are the source of novel bioactive compounds, used as therapeutic agent. Molecular docking is a computational technique use frequently, to find novel drugs targets and drugs-receptors interactions. The current study was designed to isolate and identify endophytic bacteria for the extraction of bioactive compounds. Further, to characterized extracts and to explore compounds interactions with bacterial cell wall and outer membrane synthesizing proteins. Endophytes were identified using 16s rRNA amplification technique. For bioactive compounds, solvent extraction method was followed and characterized further through GC-MS analysis. To find targets and drugs-receptors interactions, molecular docking studies and biological assays were performed. The isolated endophytes belong to five different genera namely Enterobacter, Bacillus, Erwinia, Stenotrophomonas and Pantoea. In case of antibacterial assay Stenotrophomonas maltophilia extract showed significant inhibitory zones (15.11±0.11mm and 11.3±0.16) against Staphylococcus caseolyticus and Acinetobacter baumanni, with MIC 33.3 and 50µg/mL respectively. Among the characterized fifty compounds, from endophytic bacteria "antibacterial compound" N-(5-benzyl-10b-hydroxy-2-methyl-3,6-dioxooctahydro-8H-oxazolo[3,2-α] pyrrolo[2,1c] pyrazin-2-yl)-7-methyl2,3,3a,3a1,6,6a,7,8,9,10,10a,10b-dodecahydro-1H-4λ2-indolo[4,3-fg]quinoline-9-carboxamide of bacteria Stenotrophomonas maltophilia were an excellent binder with MurF ligase active site, with binding energy of -10.2 kcal/mol. Extracts of endophytic bacteria composed of various pharmacologically active ingredients such as antibacterial compounds. Molecular docking studies provide important information regarding drug-receptor interaction, thus can be used in novel drug discovery.

Indane-1,3-diones: As Potential and Selective α-glucosidase Inhibitors, their Synthesis, in vitro and in silico Studies.

BACKGROUND: Diabetes mellitus is one of the most chronic metabolic disorders. Since past few years, our research group had synthesized and evaluated libraries of heterocyclic compounds against α and ß-glucosidase enzymes and found encouraging results. The current study comprises of evaluation of indane-1,3-dione as antidiabetic agents based on our previously reported results obtained from closely related moiety isatin and its derivatives. OBJECTIVE: A library of twenty three indane-1,3-dione derivatives (1-23) was synthesized and evaluated for α and ß-glucosidase inhibitions. Moreover, in silico docking studies were carried out to investigate the putative binding mode of selected compounds with the target enzyme. METHODS: The indane-1,3-dione derivatives (1-23) were synthesized by Knoevenagel condensation of different substituted benzaldehydes with indane-1,3-dione under basic condition. The structures of synthetic molecules were deduced by using different spectroscopic techniques, including 1H-, 13C-NMR, EI-MS, and CHN analysis. Compounds (1-23) were evaluated for α and ß-glucosidase inhibitions by adopting the literature protocols. RESULT: Off twenty three, eleven compounds displayed good to moderate activity against α- glucosidase enzyme, nonetheless, all compounds exhibited less than 50% inhibition against ß- glucosidase enzyme. Compounds 1, 14, and 23 displayed good activity against α-glucosidase enzyme with IC50 values of 2.80 ± 0.11, 0.76 ± 0.01, and 2.17 ± 0.18 µM, respectively. The results have shown that these compounds have selectively inhibited the α-glucosidase enzyme. The in silico docking studies also supported the above results and showed different types of interactions of synthetic molecules with the active site of enzyme. CONCLUSION: The compounds 1, 14, and 23 have shown good inhibition against α-glucosidase and may potentially serve as lead for the development of new therapeutic representatives.

Azaborininones: Synthesis and Structural Analysis of a Carbonyl-Containing Class of Azaborines.

An approach to access azaborininones (carbonyl-containing, boron-based heterocyclic scaffolds) using simple reagents and conditions from both organotrifluoroborates and boronic acids is described. An inexpensive, common reagent, SiO2, was found to serve as both a fluorophile and desiccant to facilitate the annulation process across three different azaborininone platforms. Computational analysis of some of the cores synthesized in this study was undertaken to compare the azaborininones with the analogous carbon-based heterocyclic systems. Computationally derived pKa values, NICS aromaticity calculations, and electrostatic potential surfaces revealed a unique isoelectronic/isostructural relationship between these azaborines and their carbon isosteres that changed based on boron connectivity. Correlation to experimentally derived data supports the computational findings.

6-Methyl-4-oxo-4H-chromene-3-carbaldehyde.

In the title compound, C(11)H(8)O(3), the benzopyran-4-one or chromone ring system is almost planar, with a maximum deviation of 0.045 (2) Å. The crystal structure is stablized by π-π inter-actions between the benzene and pyran rings of inversion-related mol-ecules stacked along the b axis, with a centroid-centroid distance of 3.5463 (12) Å

Ethyl (E)-3-(6-methyl-4-oxo-4H-chromen-3-yl)prop-2-enoate.

In the title compound, C(15)H(14)O(4), the chromone ring system is close to being planar [maximum deviation = 0.015 (2) Å]. The double bond of the ethyl prop-2-enoate chain adopts an E conformation and an intra-molecular C-H⋯O hydrogen bond generates an S6 ring. In the crystal, inversion dimers linked by pairs of C-H⋯O hydrogen bonds generate R(2) (2)(14) loops. Weak π-π inter-actions [centroid-centroid distance = 3.8493 (12) Å] also occur.

Ethyl 2-(pyridine-4-carboxamido)-4,5,6,7-tetra-hydro-1-benzothio-phene-3-carboxyl-ate.

In the title compound, C(17)H(18)N(2)O(3)S, the dihedral angles between the thio-phene ring and the ethyl ester group and the pyridine-4-carboxamide unit are 7.1 (2) and 9.47 (11)°, respectively. An intra-molecular N-H⋯O hydrogen bond generates an S(6) ring. In the crystal, inversion dimers linked by pairs of C-H⋯O hydrogen bonds between the tetra-hydro-1-benzothio-phene and the pyridine-4-carboxamide residues generate R(2) (2)(16) loops. There exists positional disorder in three methelene groups of the cyclo-hexane ring and the terminal C atom of the ethyl ester side chain in a 0.691 (14):0.309 (14) occupancy ratio.

Ethyl 2-acet-amido-4,5,6,7-tetra-hydro-1-benzothio-phene-3-carboxyl-ate.

In the title compound, C(13)H(17)NO(3)S, the dihedral angles between the thio-phene ring and the ethyl ester and acetamide groups are 5.21 (13) and 10.06 (16)°, respectively. The cyclo-hezene ring adopts a half-chair conformation. An S(6) ring is formed due to an intra-molecular N-H⋯O hydrogen bond. In the crystal, mol-ecules are linked by C-H⋯O inter-actions between the tetra-hydro-1-benzothio-phene unit and the ethyl ester group, forming C(7) chains propagating along the b-axis direction.

Diethyl 5-acetamido-3-methyl-thio-phene-2,4-dicarboxyl-ate.

The title compound, C(13)H(17)NO(5)S, is approximately planar (r.m.s. deviation for the non-H atoms = 0.055 Å). Its conformation is stabilized by N-H⋯O and C-H⋯O hydrogen bonds, which both generate S(6) rings. The crystal packing only features van der Waals contacts.

Ethyl 2-benzamido-4,5,6,7-tetra-hydro-1-benzothio-phene-3-carboxyl-ate.

The mol-ecule of the title compound, C(18)H(19)NO(3)S, adopts an approximately planar conformation: the thio-phene and phenyl rings form a dihedral angle of 8.13 (11)° while the ethyl ester group (r.m.s. deviation = 0.0217 Å) is inclined at 1.25 (14) and 8.61 (13)°, respectively, to the thio-phene and phenyl rings. An intra-molecular N-H⋯O hydrogen bond with an S(6) ring motif occurs as well as an intra-molecular S⋯O hypervalent inter-action [S⋯O = 2.7369 (18) Å]. The cyclo-hexene ring adopts a half-chair conformation and is disordered over two positions with site occupation factors of 0.641 (6) and 0.359 (6). In the crystal, inversion dimers linked by pairs of O-H⋯O hydrogen bonds generate R(2) (2)(10) loops.