Synthesis, antibacterial studies, and molecular modeling studies of 3,4-dihydropyrimidinone compounds.

The syntheses of dihydropyrimidinones (DHPMs) using solvent-free grindstone chemistry method. All the synthesized compounds exhibited significant activity against pathogenic bacteria. The current effort has been developed to obtain new DHPM derivatives that focus on the bacterial ribosomal A site RNA as a drug target. Molecular docking simulation analysis was applied to confirm the target specificity of DHPMs. The crystal structure of bacterial 16S rRNA and human 40S rRNA was taken as receptors for docking. Finally, the docking score, binding site interaction analysis revealed that DHPMs exhibit more specificity towards 16S rRNA than known antibiotic amikacin. Accordingly, targeting the bacterial ribosomal A site RNA with potential drug leads promises to overcome the bacterial drug resistance. Even though, anti-neoplastic activities of DHPMs were also predicted through prediction of activity spectra for substances (PASS) tool. Further, the results establish that the DHPMs can serve as perfect leads against bacterial drug resistance.

Synthesis of 2,6-dicarbethoxy-3,5-diaryltetrahydro-1,4-thiazine-1,1-dioxide derivatives as potent anticonvulsant agents.

An efficient synthesis of 2,6-dicarbethoxy-3,5-diaryltetrahydro-1,4-thiazine-1,1-dioxide derivatives has been achieved under aqueous medium for the first time in good to excellent yields. All the synthesized compounds were tested for anticonvulsant activity using the maximal electroshock (MES), subcutaneous pentylenetetrazole (scPTZ) screens, which are the most broadly employed seizure models for early identification of candidate anticonvulsants. Their neurotoxicity was determined applying the rotarod test. Seven compounds 4a, 4d, 4f, 4h, 4o, 4p and 4q showed promising anticonvulsant activities in both models employed for anticonvulsant evaluation. The most active compound 4d showed the MES-induced seizures with ED50 value of 10.2 mg/kg and TD50 value of 288.6 mg/kg after intraperitoneal injection to mice, which provided compound 4d with a protective index (TD50/ED50) of 28.3 in the MES test.

A new prenylated acetophenone from the root bark of Derris indica.

A new acetophenone, 1-[2,4-dihydroxy-5-(3-methylbut-2-enyl)phenyl]ethanone (1) was isolated from the root bark of Derris indica, along with 3,7,-dimethoxy-3',4'-methylenedioxyflavone (desmethoxykanugin) (2), 5-methoxyfurano[4",5":6,7]flavone (pinnatin) (3), and 3'-hydroxyfurano[4",5":7,8]flavone (pongol) (4). The structures of these compounds were established by means of chemical and spectral studies. The occurrence of this prenylated acetophenone in D. indica is of biogenetic and chemotaxonomic significance.

Synthesis and in vitro antitubercular activity of 4-aryl/alkylsulfonylmethylcoumarins as inhibitors of Mycobacterium tuberculosis.

A series of 4-aryl/alkylsulfonylmethylcoumarins have been synthesized and screened for in vitro antitubercular activity against Mycobacterium tuberculosis H(37)Rv (MTB). Four of the compounds showed MIC in the range of 0.78-3.13 µg/mL proving their potential activity.

Isoxazoles incorporated N-substituted decahydroquinolines: a precursor to the next generation antimicrobial drug.

We report here a simple entry into N-substituted decahydroisoxazoloquinoline system with substituents at position 3 and 4 from the readily available substrates for the first time. The synthesized isoxazoloquinolines were evaluated against six bacterial and four fungal strains. The results suggest that the decahydroisoxazolo[4,3-c]quinoline scaffold has the potential to be developed into therapeutically useful antimicrobial agents.

Design and synthesis of 3,5-diarylpiperidin-2,6-diones as anticonvulsant agents.

The present Letter describes a one-pot multi-component method that allows the efficient and mild preparation of 3,5-diphenylpiperidin-2,6-dione and a new series of 3,5-diarylpiperidin-2,6-dione derivatives from ethyl 2-arylacetates, formaldehyde and ammonia/aliphatic/aromatic amines. The structures of the compounds were elucidated by IR, NMR spectroscopic data and microanalyses. The anticonvulsant activities of these compounds were evaluated by maximal electroshock seizure test and were also evaluated for motor impairment. Among the synthesized compounds, 5a, 5b, 5d, and 5e could be considered potentially the most useful and safe therapeutic compound and 5g, 5i, 5j, 5m, and 5o exhibit potent activities.