nan Chandra

Microwave assisted synthesis of dihydrobenzo[4,5]imidazo[1,2-a]pyrimidin-4-ones; synthesis, in vitro antimicrobial and anticancer activities of novel coumarin substituted dihydrobenzo[4,5]imidazo[1,2-a]pyrimidin-4-ones.

The present article describes the synthesis of dihydrobenzo[4,5]imidazo[1,2-a]pyrimidin-4-one (2a-h) under microwave irradiation. The product was obtained in excellent yield (74-94%) in a shorter reaction time (2 min). These molecules (2a, b) further reacted with various substituted 4-bromomethylcoumarins (3a-f) to yield a new series of coumarin substituted dihydrobenzo[4,5]imidazo[1,2-a]pyrimidin-4-ones (4a-h). The structure of all the synthesized compounds were confirmed by spectral studies and screened for their in vitro antibacterial activity against three Gram-positive bacteria viz., Staphylococcus aureus, Enterococcus faecalis, Streptococcus mutans and three Gram-negative bacteria viz., Escherichia coli, Klebsiella pneumonia, Pseudomonas aeruginosa and antifungal activity against Candida albicans, Aspergillus niger, Aspergillus fumigatus, Aspergillus flavus, Fusarium oxysporum, Penicillium chrysogenum and anticancer activity against Daltons Ascitic Lymphoma (DAL) cell line. In general, all the compounds possessed better antifungal properties than antibacterial properties. The coumarin substituted dihydrobenzo[4,5]imidazo[1,2-a]pyrimidin-4-one (4g) (R = i-Pr, R₁ = 6-Cl) was found to be the most potent cytotoxic compound (88%) against Daltons Ascitic Lymphoma cell line at the concentration of 100 μg/mL.

Synthesis and characterization of novel oxazines and demonstration that they specifically target cyclooxygenase 2.

In the present study, we used solution combustion synthesis-bismuth oxide (Bi2O3) as catalyst for the simple and efficient synthesis of 1,2-oxazine based derivatives of 6-fluoro-3-(piperidin-4-yl)benzo[d]isoxazoles, 1-arylpiperazine and carbazoles. (4aR,8aR)-4-(4-Methoxyphenyl)-3-((4-(4-methoxyphenyl)piperazin-1-yl)methyl)-4a,5,6,7,8,8a-hexahydro-4H-benzo[e][1,2]oxazine was found to be the most potent compound with a high degree of selectivity in inhibition towards COX2 (1.7 μM) over COX1 (40.4 μM) demonstrating the significance of 1,2-oxazine derivatives in developing COX2 specific inhibitors. Molecular docking analyses demonstrated that an isoleucine residue in the active site of COX1 is responsible for lower affinity to COX1 and increased potency towards COX2. Overall, our study reveals that the new 1,2-oxazine-based small molecules qualify as lead structures in developing COX2-specific inhibitors for anti-inflammatory therapy.

Synthesis of N1 and N2 coumarin substituted 1,2,3-triazole isomers via click chemistry approach

ABSTRACT The synthesis of N1 and N2 coumarin substituted 1,2,3-triazole isomers from terminal alkynes, sodium azide, and 4-bromomethylcoumarins in the presence of triethylamine as a base and CuI as a catalyst in good yield are reported. The molecular structure of compounds 3g and 5d are established by single-crystal analysis. GRAPHICAL ABSTRACT

A Nano-MgO and Ionic Liquid-Catalyzed ‘Green’ Synthesis Protocol for the Development of Adamantyl-Imidazolo-Thiadiazoles as Anti-Tuberculosis Agents Targeting Sterol 14α-Demethylase (CYP51)

In this work, we describe the ‘green’ synthesis of novel 6-(adamantan-1-yl)-2-substituted-imidazo[2,1-b][1,3,4]thiadiazoles (AITs) by ring formation reactions using 1-(adamantan-1-yl)-2-bromoethanone and 5-alkyl/aryl-2-amino1,3,4-thiadiazoles on a nano material base in ionic liquid media. Given the established activity of imidazothiadiazoles against M. tuberculosis, we next examined the anti-TB activity of AITs against the H37Rv strain using Alamar blue assay. Among the tested compounds 6-(adamantan-1-yl)-2-(4-methoxyphenyl)imidazo[2,1-b][1,3,4]thiadiazole (3f) showed potent inhibitory activity towards M. tuberculosis with an MIC value of 8.5 μM. The inhibitory effect of this molecule against M. tuberculosis was comparable to the standard drugs such as Pyrazinamide, Streptomycin, and Ciprofloxacin drugs. Mechanistically, an in silico analysis predicted sterol 14α-demethylase (CYP51) as the likely target and experimental activity of 3f in this system corroborated the in silico target prediction. In summary, we herein report the synthesis and biological evaluation of novel AITs against M. tuberculosis that likely target CYP51 to induce their antimycobacterial activity.

Novel 5-functionalized-pyrazoles: Synthesis, characterization and pharmacological screening

In the present study a series of O-substituted pyrazoles 7(a-f) and N-substituted pyrazoles 9(a-f) were synthesized via phase-transfer catalyzed reaction of ethyl 5-(bromomethyl)-1,3-diphenyl-1H-pyrazole-4-carboxylate 5 with various oxygen and nitrogen containing compounds in presence of tetrabutylammonium bromide (TBAB) in THF. The compound 5 was obtained by the efficient bromination with N-bromosuccinimide (NBS) in presence of a catalytic amount of azoiso-bis-butyro nitrile (AIBN) in refluxing CCl4. The synthesized compounds were evaluated for their in vitro antimicrobial and antidiabetic activity and were compared with standard drugs. Among the synthesized compounds, compound 9b emerged as an excellent antimicrobial and antidiabetic agent. Newly synthesized compounds were characterized by analytical and spectral (IR, (1)H NMR, (13)C NMR and LC-MS) methods.

One-Pot Tandem Synthesis of Tetrasubstituted Pyrazoles via 1,3-Dipolar Cycloaddition Between Aryl Hydrazones and Ethyl But-2-ynoate

Abstract 1,3,4,5-Tetrasubstituted pyrazoles are rapidly and regioselectively synthesized in a one-pot, three-step sequence consisting of condensation, nitrilimine generation, and cycloaddition using mercuric acetate. Newly synthesized compounds were characterized by spectral studies. Regiochemistry of compounds 6a and 8a was determined as 1,4- and 1,5-regioisomers respectively by X-ray crystallography. GRAPHICAL ABSTRACT

Molecular docking studies of benzimidazopyrimidine and coumarin substituted benzimidazopyrimidine derivatives: As potential human Aurora A kinase inhibitors

Protein kinases are important drug targets in human cancers, inflammation and metabolic diseases. Docking studies was performed for all the benzimidazopyrimidine and coumarin substituted benzimidazopyridimine derivatives with human Aurora A kinase target (3FDN) employing flexible ligand docking approach by using AutoDock 4.2. All the compounds were found to have minimum binding energy ranging from -6.26 to -9.29 kJ/mol. Among the molecules tested for docking study, 10-(6-Bromo-2-oxo- 2H-chromen-4-ylmethyl)-2-isopropyl-10H-benzo[4,5]imidazo[1,2-a]pyrimidin-4-one (2k) showed minimum binding energy (-9.29 kJ/mol) with ligand efficiency of -0.31. All the ligands were docked deeply within the binding pocket region of 3FDN showing hydrogen bonds with Ala 213 and Asn 261. The docking study results showed that these derivatives are excellent inhibitor of human Aurora A kinase target; and also all these docked compounds have good inhibition constant, vdW + Hbond + desolv energy with best RMSD value.

A simple and efficient synthesis of substituted pyrazoles

A novel route for the formation of 3-aryl-1-phenyl-1H-pyrazoles was discovered upon the reaction of 3-aryl-1-phenyl-4,5-dihydro-1H-pyrazole-5-carbonitrile with potassium hydroxide in the presence of a phase transfer catalyst (tetrabutylammonium bromide) in THF as a solvent, and a single crystal X-ray study is reported.

3-(4-Meth­oxy­phen­yl)-5-methylisoxazole-4-carb­oxy­lic acid

In the title compound, C12H11NO4, the dihedral angle between the benzene and isoxazole rings is 42.52 (8)°. The carboxylic acid group is close to being coplanar with the isoxazole ring [dihedral angle = 5.3 (2)°]. In the crystal, inversion dimers linked by pairs of O—H⋯O hydrogen bonds generate R 2 2(8) loops.

Ethyl 5-methyl-3-phenyl-isoxazole-4-carboxyl-ate.

In the title compound, C13H13NO3, the dihedral angle between the phenyl and isoxazole rings is 43.40 (13)°. The ethoxycarbonyl group is rotated out of the plane of the isoxazole ring by 16.2 (13)°.