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Fulltext Rational design and synthesis of novel diphenyl ether derivatives as antitubercular agents

Kar SS, Bhat G V, Rao PP, Shenoy VP, Bairy I, Shenoy GG

Drug Des Devel Ther, 2016;10:2299-310.
PMID: 27486307 DOI: 10.2147/DDDT.S104037

A series of triclosan mimic diphenyl ether derivatives have been synthesized and evaluated for their in vitro antitubercular activity against Mycobacterium tuberculosis H37Rv. The binding mode of the compounds at the active site of enoyl-acyl carrier protein reductase of M. tuberculosis has been explored. Among them, compound 10b was found to possess antitubercular activity (minimum inhibitory concentration =12.5 µg/mL) comparable to triclosan. All the synthesized compounds exhibited low levels of cytotoxicity against Vero and HepG2 cell lines, and three compounds 10a, 10b, and 10c had a selectivity index more than 10. Compound 10b was also evaluated for log P, pKa, human liver microsomal stability, and % protein binding, in order to probe its druglikeness. Based on the antitubercular activity and druglikeness profile, it may be concluded that compound 10b could be a lead for future development of antitubercular drugs.
Fulltext Modified uremic rat model - A tool for uremic studies in rats

Iype M, Upadhya S, Upadhya S, Bhat G

Indian J Clin Biochem, 2008 Oct;23(4):401-3.
PMID: 23105796 DOI: 10.1007/s12291-008-0088-1

Experimental model of chronic renal failure in rats have been described by many authors and has also been widely used in various studies. Many of these methods used highly sophisticated instruments which was difficult in our settings. The resection model was ideal in our experimental set-up, but this model had the risk of excessive bleeding and hypovolemia. In our study we used a combination of partial resection and ligation of the renal artery to create two models of stable uremia A and Moderate uremia B. Severe uremia. Both these models were compared with a sham operated group which served as controls. Following surgical procedure, the development of uremia was monitored by serial estimation of blood urea and serum creatinine levels that were measured at regular intervals (bi-weekly). From two weeks onwards the animals in the experimental group showed a significant elevation in the serum urea levels and a consistent elevation in the serum creatinine levels upto eight weeks when compared to the animals in the sham operated group. We established a modified method of producing renal failure which can be maintained for a period of six weeks. This model is simple, reproducible and less complicated that can be used for several studies relating to renal failure in the field of research.
Synthesis, evaluation, molecular docking, and molecular dynamics studies of novel N-(4-[pyridin-2-yloxy]benzyl)arylamine derivatives as potential antitubercular agents

Verma R, Boshoff HIM, Arora K, Bairy I, Tiwari M, Varadaraj BG, et al.

Drug Dev Res, 2020 May;81(3):315-328.
PMID: 31782209 DOI: 10.1002/ddr.21623

A new series of novel triclosan (2,4,4'-trichloro-2'-hydroxydiphenylether) analogues were designed, synthesized, and screened for their in vitro antimycobacterial and antibacterial activities. Most of the compounds showed significant activity against Mycobacterium tuberculosis H37Rv strain with minimum inhibitory concentration (MIC) values in 20-40 μM range in GAST/Fe medium when compared with triclosan (43 μM) in the first week of assay, and after additional incubation, seven compounds, that is, 2a, 2c, 2g, 2h, 2i, 2j, and 2m, exhibited MIC values at the concentration of 20-40 μM. The compounds also showed more significant activity against Bacillus subtilis and Staphylococcus aureus. The synthesized compounds showed druggable properties, and the predicted ADME (absorption, distribution, metabolism, and excretion) properties were within the acceptable limits. The in silico studies predicted better interactions of compounds with target protein residues and a higher dock score in comparison with triclosan. Molecular dynamics simulation study of the most active compound 2i was performed in order to further explore the stability of the protein-ligand complex and the protein-ligand interaction in detail.
Fulltext Esophageal ulcer in a HIV-seropositive patient co-infected by herpes simplex and cytomegalovirus

Srilatha PS, Suvarna N, Gupta A, Bhat G

Indian J Pathol Microbiol, 2011 Jan-Mar;54(1):219-20.
PMID: 21393929 DOI: 10.4103/0377-4929.77420
In silico studies, synthesis and anticancer activity of novel diphenyl ether-based pyridine derivatives

Verma R, Bairy I, Tiwari M, Bhat GV, Shenoy GG

Mol Divers, 2019 Aug;23(3):541-554.
PMID: 30430400 DOI: 10.1007/s11030-018-9889-1

A series of novel 2-amino-4-(3-hydroxy-4-phenoxyphenyl)-6-(4-substituted phenyl) nicotinonitriles were synthesized and evaluated against HepG2, A-549 and Vero cell lines. Compounds 3b (IC50 16.74 ± 0.45 µM) and 3p (IC50 10.57 ± 0.54 µM) were found to be the most active compounds against A-549 cell line among the evaluated compounds. Further 3b- and 3p-induced apoptosis was characterized by AO/EB (acridine orange/ethidium bromide) nuclear staining method and also by DNA fragmentation study. A decrease in cell viability and initiation of apoptosis was clearly evident through the morphological changes in the A-549 cells treated with 3b and 3p when stained with this method. Fragmentation of DNA into nucleosomes was observed which further confirmed the cell apoptosis in cells treated with compound 3b. Flow cytometry studies confirmed the cell cycle arrest at G2/M phase in A549 cells treated with compound 3b. Further in silico studies performed supported the in vitro anticancer activity of these compounds as depicted by dock score and binding energy values.
Fulltext Identification of multiple strains of Porphyromonas gingivalis using heteroduplex polymerase chain reaction in varying severity of chronic periodontitis

Kulkarni MR, Bhat KG, Thomas BS, Bhat GS, Kulkarni RD

Indian J Med Microbiol, 2018 5 8;36(1):81-86.
PMID: 29735832 DOI: 10.4103/ijmm.IJMM_17_434

Aim: Research has demonstrated that there are multiple strains of Porphyromonas gingivalis with varying potency to cause periodontal disease. The current study aims at using heteroduplex polymerase chain reaction (PCR) to detect the strain diversity of P. gingivalis in periodontitis lesions of varying severity in a sample of the Indian population.
Materials and Methods: Subgingival plaque samples were collected from 60 individuals with varying severity of chronic periodontitis and 30 individuals with a clinically healthy periodontium. The samples were subjected to PCR analysis to identify P. gingivalis, followed by heteroduplex analysis to identify the strain diversity in a given sample. Bacterial culture was carried out as a comparative standard.
Results: Of the 56 samples that were positive for P. gingivalis by PCR, 54 samples yielded eight different heteroduplex patterns. Analysis of these patterns indicated that two strains of P. gingivalis were present in 41 individuals (45.6%) and three strains were present in 13 individuals (14.4%). Detection of P. gingivalis by PCR was significantly more in the periodontitis group as compared to the healthy group.
Conclusions: Species-specific PCR and heteroduplex analysis provide a simple and accurate method to analyse the strain diversity of P. gingivalis. P. gingivalis was detected in both healthy periodontal sites as well as sites with periodontitis. The presence of two or three P. gingivalis strains was seen in 60% of the samples.