Bhimapaka China Raju

A Novel Approach for C–C, C–N, and C–O Bond Formation Reactions: A Facile Synthesis of Benzophenazine, Quinoxaline, and Phenoxazine Derivatives via Ring Opening of Benzoxepines

A new one-pot protocol has been developed for the synthesis of benzophenazine, quinoxaline, and phenoxazine derivatives by the reaction of benzoxepine-4-carboxylates with benzene-1,2-diamines, ethane-1,2-diamine, and 2-aminophenols in the presence of Bi(OTf)3 (5 mol %) under mild conditions in very good yields. The present protocol opens a new way for C-C, C-N, and C-O bond-formation reactions in a single-step process. The structural assignment was confirmed by X-ray analysis.

New antihyperglycemic, α-glucosidase inhibitory, and cytotoxic derivatives of benzimidazoles

Glycosidases play an important role in a wide range of physiological and pathological conditions, and have become potential targets for the discovery and development of agents useful for the treatment of diseases such as diabetes, cancer, influenza, and even AIDS. In this study, several benzimidazole derivatives were prepared from o-phenylenediamine and aromatic and heteroaromatic carboxaldehydes in very good yields, using PdCl2(CH3CN)2 as the most efficient catalyst. Synthesized compounds were assayed for their activity on yeast and rat intestinal α-glucosidase inhibition and cytotoxic activity against colon carcinoma cell line HT-29. Compound 3e exhibited 95.6% and 75.3% inhibition of yeast and rat intestinal α-glucosidase enzyme, while showing 74.8% cytotoxic activity against the HT-29 cell line at primary screening concentrations of 2.1 mM for yeast and rat intestinal α-glucosidase enzyme and 0.2 mM for cytotoxic activity against the HT-29 cell line, respectively. Compound 3c displayed 76% and 34.4% inhibition of yeast and rat intestinal α-glucosidase enzyme, and 80.4% cytotoxic activity against the HT-29 cell line at similar primary screening concentrations. The IC50 value for the most potent intestinal α-glucosidase inhibitor compound 3e was found to be 99.4 μM. The IC50 values for the most active cytotoxic compounds 3c and 3e were 82 μM and 98.8 μM, respectively. Both compounds displayed significant antihyperglycemic activity in starch-induced postprandial hyperglycemia in rats. This is the first report assigning yeast and rat intestinal α-glucosidase enzyme inhibition, cytotoxic activity against the HT-29 cell line, and antihyperglycemic activity to benzimidazole compounds 3c and 3e.

Synthesis and anti-mycobacterial activity of 2-chloronicotinaldehydes based novel 1H-1,2, 3-triazolylbenzohydrazides

1H-1,2,3-Triazolylbenzohydrazides (6a-h and 11a-l) were synthesized from 2-chloronicotinaldehydes and evaluated for anti-mycobacterial activity against Mycobacterium tuberculosis H37Rv strain (ATCC-27294). Seven compounds 6b, 6e,f, 11d, 11h, 11j and 11l displayed potent anti-mycobacterial activity (MIC 2.8-6.2 μM). Potent anti-mycobacterial compounds were chosen for cytotoxicity studies by MTT protein assay against normal cell lines (PBMC and Raw 264.7) and shown low cytotoxicity. This is the first Letter assigning anti-mycobacterial activity, cytotoxicity and structure activity relationship for 1H-1,2,3-triazolylbenzohydrazides.

Synthesis, pharmacological activities and molecular docking studies of pyrazolyltriazoles as anti-bacterial and anti-inflammatory agents

A series of novel pyrazolyl alcohols (5a-h), pyrazolyl azides (6a-h), and pyrazolyltriazoles (8a-h, 10a-p and 12a-l) were prepared and evaluated for their bioactivity (anti-bacterial and anti-inflammatory) profile. The compound 5c displayed the potent anti-bacterial activity against Micrococcus luteus (MIC 3.9 and MBC 7.81µg/mL). In vitro anti-inflammatory activity data denoted that compound 8b is effective among the tested compounds against IL-6 (IC50 6.23μM). Docking analysis of compounds 5f, 8a-b, 8e-f and 8h displayed high binding energies for the compounds 8a-b and 8h towards TNF-α dimer (2AZ5 protein) and IL-6 (1ALU protein). In vivo anti-inflammatory activity of compounds 8b and 8h with respect to LPS induced mice model indicated that compound 8h showed significant reduction in TNF-α.

La(OTf) 3 catalyzed reaction of salicylaldehyde phenylhydrazones with β-ketoesters and activated alkynes: facile approach for the preparation of chromenopyrazolones

A facile approach has been developed for the preparation of chromenopyrazolones (5a–o, 7a–k) by the reaction of salicylaldehyde phenylhydrazones (3a–o) with β-ketoesters (4a, 4f–g) and activated alkynes (6a–e) in the presence of La(OTf)3 with good yields. However, the reaction of salicylaldehyde phenylhydrazones (3a, 3c, 3j–k, 3n) with ethyl 4-chloro-3-oxobutanoate (4e) underwent cyclization with reductive dechlorination and provided the methyl chromenopyrazolones instead of chloromethyl chromenopyrazolones. The present solvent free protocol provided the novel heterocyclic compounds.

New convenient approach for the synthesis of benzyl 2H-chromenones and their α-amylase Inhibitory, ABTS.+ scavenging activities.

Series of new benzyl 2H-chromenones 6a-n was synthesized by Pechmann condensation of substituted benzyl resorcinols 2a-c and 3a with various β-ketoesters such as ethyl 3-oxobutanoate, ethyl 3-oxo-3-phenylpropanoate, ethyl 4- chloro-3-oxobutanoate, ethyl 4,4,4-trifluoro-3-oxobutanoate and ethyl 2-chloro-3-oxobutanoate 5a-e in very good yields. Synthesized compounds 6a-n were screened for their α-amylase inhibitory, and ABTS.+ scavenging activities. In the present series of compounds, compound 8-benzyl-7-hydroxy-4-phenyl-2H-chromen-2-one 6c and 8-benzyl-7-hydroxy-4- methyl-2H-chromen-2-one 6a were most potent ABTS.+ radical scavenging and α-amylase inhibitor. Although compound 6,8-dibenzyl-7-hydroxy-4-(trifluoromethyl)-2H-chromen-2-one 6h displayed potent ABTS.+ free radical scavenging potential, it was found poor in inhibiting pancreatic α-amylase.

Facile construction of novel heterocyclic compounds: three-component, one-pot synthesis of 2-hydroxybenzoyl-1,2-dihydropyridine-3-carboxylates, ketones, pyridone-3-carboxylates and benzopyrido-1,3-oxazole-4-carboxylates

A facile method has been developed for the preparation of novel heterocyclic compounds by the reaction of 3-formylchromones, benzylamines, and 2-aminophenols with 3-oxobutanoates. 3-Oxobutanoates bearing trifluoro or trichloro substituents and trifluoro containing 1,3-diketones facilitated the reaction. The reaction proceeds via a Schiff base mediated Michael addition followed by the selective addition of enamine to the carbonyl group adjacent to the trihalo group due to a strong electron withdrawing effect. The present three-component, one-pot protocol provided heterocyclic compounds without a catalyst.

Condensation of Ortho-phenylenediamines and Phenylhydrazines with Ethyl 4-Chloro-3-oxobutanoate: A Facile Approach for the Synthesis of Substituted 1H-Benzimidazoles, Pyrazolones, and Pyrazoles

Abstract Substituted 1H-benzimidazoles, pyrazolones, and pyrazoles have been synthesized by the condensation of ortho-phenylenediamines and phenylhydrazines, respectively, with ethyl 4-chloro-3-oxobutanoate in good yields. The present approach is novel, straightforward, and being reported for the first time with ethyl 4-chloro-3-oxobutanoate. GRAPHICAL ABSTRACT

Anti-proliferative, structure–activity relationship of pyridinylchalcones and chromanones

A series of pyridinylchalcones 3a–q, chromanones 4a–q were prepared and screened for their in vitro anti-proliferative activity against four human cancer cell lines viz., cervical (HeLa), lung adenocarcinoma (A549), prostate (DU-145) and breast (MDA-MB-231). Pyridinylchalcones 3a-q and chromanones 4a-q exhibited IC50 values in the range of 5.9–289 µM. Compound 3e exhibited an IC50 of 5.9 µM and also increased caspase-3 activity to ~ 2.7-fold at 10 µM concentration in HeLa cell line. Cell cycle analysis further confirmed the apoptotic effects of 3e due to a substantial increase in cells arrested at sub-G1 phase of cell cycle. Further, the loss of mitochondrial membrane potential in 3e treated cells indicates that the intrinsic pathway of apoptosis might be responsible in 3e induced apoptosis.Graphical AbstractPyridinylchalcones, chromanones were screened for their in vitro anti-proliferative activity against four human cancer cell lines by the standard 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay method. Pyridinylchalcones and chromanones exhibited IC50 values in the range of 5.9–289 µM. Compound 3e exhibited an IC50 of 5.9 µM and also increased caspase-3 activity to ~2.7-fold at 10 µM concentration in HeLa cell line

Convenient synthesis of 4H-chromenyl-tetrahydro-2H-pyrancarboxylates and cleavage of chromone and pyran rings leading to 5-(2-hydroxybenzoyl)-2-(trifluoromethyl)-1,2-dihydropyridine-3-carboxylates

ABSTRACT 4H-Chromenyl-tetrahydro-2H-pyrancarboxylates 3a–k have been conveniently prepared by the reaction of 3-formylchromones 1a–k and ethyl 4,4,4-trifluoro-3-oxobutanoate 2a with good yields. Thus obtained 4H-chromenyl-tetrahydro-2H-pyrancarboxylates 3a–k were reacted with amines 4a–e to provide series of 5-(2-hydroxybenzoyl)-2-(trifluoromethyl)-1,2-dihydropyridine-3-carboxylates 5a–o. The reaction proceeded via Michael addition (C-N bond formation) and followed by cleavage of chromone and pyran rings (C-O bond cleavage) in one pot. GRAPHICAL ABSTRACT