Lingala Suresh

An efficient one-pot synthesis of thiochromeno[3,4-d]pyrimidines derivatives: Inducing ROS dependent antibacterial and anti-biofilm activities.

An efficient synthesis of thiochromeno[3,4-d]pyrimidine derivatives has been achieved successfully via a one-pot three-component reaction of thiochrome-4-one, aromatic aldehyde and thiourea in the presence of 1-butyl-3-methyl imidazolium hydrogen sulphate [Bmim]HSO4. This new protocol has the advantages of environmental friendliness, high yields, short reaction times, and convenient operation. Furthermore, among all the tested derivatives, compounds 4b and 4c exhibited promising antibacterial, minimum bactericidal concentration and anti-biofilm activities against Staphylococcus aureus MTCC 96, Staphylococcus aureus MLS16 MTCC 2940 and Bacillus subtilis MTCC 121. The compound 4c also showed promising intracellular ROS accumulation in Staphylococcus aureus MLS16 MTCC 2940 comparable to that of ciprofloxacin resulting in apoptotic cell death of the bacterium.

An expeditious four-component domino protocol for the synthesis of novel thiazolo[3,2-a]thiochromeno[4,3-d]pyrimidine derivatives as antibacterial and antibiofilm agents.

An efficient domino protocol has been developed for the synthesis of new pyrimidine scaffolds, through a one-pot four-component cascade transformation via [Bmim]HSO4 ionic liquid mediated reaction, using an equimolar mixture of thiochroman-4-one, benzaldehyde, thiourea and 3-bromo-1-phenylpropan-1-one leading to the formation of a double electrophilic pyrimidine-2(5H)-thione intermediate. The intermediate regioselectively undergoes cyclization through intramolecular NH bond activation followed by CS bond formation leading to highly functionalized thiazolo[3,2-a]thiochromeno[4,3-d]pyrimidines. The ionic liquid operates efficiently under mild conditions. The recyclability and scope for recovery of the ionic liquid makes this protocol environmentally benign. Further, the compounds 5d, 5g and 5k showed promising antimicrobial activity against the tested Gram-positive bacterial strains. Among them, the compound 5d was identified as a lead molecule exhibiting promising anti-biofilm activity towards Staphylococcus aureus MTCC 96, Bacillus subtilis MTCC 121, Staphylococcus aureus MLS16 MTCC 2940 and Micrococcus luteus MTCC 2470 with IC50 values of 2.1, 1.9, 2.4 and 5.3μg/mL, respectively. Further, the compound 5d showed increased levels of intracellular ROS accumulation in Staphylococcus aureus MTCC 96 suggesting that oxidative stress resulted in bacterial cell lysis and death.

Ionic liquid-promoted multicomponent synthesis of fused tetrazolo[1,5-a]pyrimidines as α-glucosidase inhibitors.

A simple and facile synthesis of fused tetrazolo[1,5-a]pyrimidine derivatives based on the multicomponent reaction of acetophenone, dimethylformamidedimethylacetal and 5-aminotetrazole is described. A green chemical synthesis has been achieved by using1-butyl-3-methylimidazolium hydrogen sulfate [Bmim]HSO4 ionic liquid as a reusable medium. Short synthetic route, operational simplicity, good yields, eco-friendliness and recyclability of the ionic liquid are the advantages of this method. The synthesized compounds were screened for α-glucosidase inhibitory activity using yeast maltase (MAL12) as a model enzyme. Inhibition and kinetic studies have shown that compounds 4d and 4g are found to be active showing comparable inhibitory potency with acarbose. Further docking studies of the derivatives with MAL12 homology model identified a similar binding mode consistent with the binding of acarbose. These studies along with in silico predicted ADMET properties suggest that these molecules could represent a new scaffold that may be useful for the development of new anti-diabetic drugs.

Design, synthesis and evaluation of novel pyrazolo-pyrimido[4,5-d]pyrimidine derivatives as potent antibacterial and biofilm inhibitors

An efficient four-component reaction of 6-amino-1,3-dimethyluracil, N,N-dimethylformamide dimethylacetal, 1-phenyl-3-(4-substituted-phenyl)-4-formyl-1H-pyrazoles and aromatic amines was conducted in the presence of [Bmim]FeCl4 ionic liquid as a promoting medium. This strategy provided a convenient route without any additional catalyst or metal salt under mild conditions. All the synthesized pyrazolo-pyrimido[4,5-d]pyrimidines derivatives were evaluated for their antibacterial, minimum bactericidal concentration (MBC), biofilm inhibition, intracellular ROS accumulation and protein leakage activities. The results revealed that among all the screened derivatives, the compounds 5c, 5i, 5l and 5m were quite promising with MIC values ranging between 3.9 and 15.6μg/mL, while the MBC values were 2-fold the antibacterial activity values. The biofilm inhibition activity revealed that the compounds 5l and 5m exhibited promising activity with IC50 values ranging between 1.8 and 8.2μg/mL. It was observed that at a concentration of 0.5μg/mL, the compound 5l treated biofilms of Micrococcus luteus showed increased levels of intracellular ROS accumulation. Further, the protein leakage study revealed that the Micrococcus luteus cells treated with compound 5l caused membrane permeability which resulted in protein leakage and subsequent bacterial cell death.

Eu2O3 modified CeO2 nanoparticles as a heterogeneous catalyst for an efficient green multicomponent synthesis of novel phenyldiazenyl-acridinedione-carboxylic acid derivatives in aqueous medium

A green and highly efficient protocol has been developed for the synthesis of phenyldiazenyl-acridinedione-carboxylic acids by a one-pot multicomponent coupling of 1,3-dicarbonyl compounds, 4-hydroxy-3-methoxy-5-(substituted-phenyl-diazenyl)-benzaldehydes and glycine using europium modified ceria nanoparticles as the catalyst in aqueous medium. An environmentally benign reaction procedure, a wide diversity of products, excellent yields and reusability of the catalyst make the present method extremely advantageous for the synthesis of phenyldiazenyl-acridinedione-carboxylic acids. The formation, size and oxidation state of the metal ions present in the nano-europium modified ceria is confirmed by powdered-XRD, TEM and XPS techniques.

Heterogeneous recyclable nano-CeO2 catalyst: efficient and eco-friendly synthesis of novel fused triazolo and tetrazolo pyrimidine derivatives in aqueous medium

A ceria nano catalyst was used for the one-pot, multi-component condensation reaction of benzoylacetonitrile, aromatic aldehydes and 5-aminotriazole/5-aminotetrazole, and proceeds via C–C and C–N bond formation to deliver the desired triazolo/tetrazolo[1,5-a]pyrimidine derivatives. This protocol provides cleaner conversion with high selectivity and shorter reaction times. The CeO2 nanoparticles were prepared by a simple coprecipitation method and characterized using XRD, TEM, and XPS techniques.

α-Glucosidase inhibitory activity, molecular docking, QSAR and ADMET properties of novel 2-amino-phenyldiazenyl-4H-chromene derivatives

α-Glucosidase inhibitory activity, molecular docking, QSAR and ADMET properties of novel 2-amino-phenyldiazenyl-4H-chromene derivatives Onkara Perumal, Sagar Vijay Kumar Peddakotla, Lingala Suresh, G.V.P. Chandramouli* and Y. Pydisetty* Department of Biotechnology, National Institute of Technology, Warangal 506 004, Telangana, India; Department of Chemistry, National Institute of Technology, Warangal 506 004, Telangana, India; Department of Chemical Engineering, National Institute of Technology, Warangal, 506 004, Telangana, India

Design, synthesis, in vitro antimicrobial and cytotoxic evaluation of novel 1,2,3-selena/thiadiazolyltetrazole derivatives

A new series of 2,5-disubstituted tetrazoles and 1,2,3-selena/thiadiazolyl-2H-tetrazole derivatives were synthesized and evaluated for their in vitro antimicrobial and cytotoxic activities against pathogenic strains. The preliminary screening results indicated that some of the compounds demonstrated moderate to good antibacterial and antifungal activities, comparable to the first-line drugs. Compounds 6a and 6b exhibited pronounced cytotoxicity against Hep G2 and MCF-7 cell lines. The chemical structures of all the newly synthesized compounds were characterized by means of spectral and elemental analyses.