600173-41-9Relevant academic research and scientific papers
Synthesis, biological evaluation and molecular dynamics simulation studies of novel diphenyl ethers
Bhat, Pritesh,Cinu Thomas, A.,Kar, Sidhartha S.,Khade, Amol B.,Shenoy, G. Gautham,Tiwari, Ashutosh,Tiwari, Mradul,Vandana, K. E.,Varadaraj Bhat, G.
, p. 256 - 270 (2020/03/10)
A series of novel N-(1-(3-hydroxy-4-phenoxyphenyl)-3-oxo-3-phenylpropyl)acetamides and N-(3(3-hydroxy-4phenoxyphenyl)-3-oxo-1-phenylpropyl) acetamides were designed, synthe-sized, and evaluated against HepG2, A-549, MCF-7 and Vero cell lines. Among the te
Design, synthesis, in silico and in vitro evaluation of novel diphenyl ether derivatives as potential antitubercular agents
Tiwari, Ashutosh Prasad,Sridhar,Boshoff, Helena I.,Arora, Kriti,Gautham Shenoy,Vandana,Varadaraj Bhat
, p. 1265 - 1279 (2019/11/03)
Abstract: Diphenyl ether derivatives inhibit mycobacterial cell wall synthesis by inhibiting an enzyme, enoyl-acyl carrier protein reductase (InhA), which catalyses the last step in the fatty acid synthesis cycle of genus Mycobacterium. To select and validate a protein crystal structure of enoyl-acyl carrier protein reductase of Mycobacterium tuberculosis for designing inhibitors using molecular modelling, a cross-docking and correlation study was performed. A series of novel 1-(3-(3-hydroxy-4-phenoxyphenyl)-5-phenyl-4,5-dihydro-1H-pyrazol-1-yl) ethan-1-ones were synthesized from this model and screened for their antitubercular activity against M. tuberculosis H37Rv. Compound PYN-8 showed good antitubercular activity on M. tuberculosis H37Rv (MIC = 4–7?μM) and Mycobacterium bovis (% inhibition at 10?μM = 95.91%). Cytotoxicity of all the synthesized derivatives was assessed using various cell lines, and they were found to be safe. Structure of PYN-8 was also confirmed by single-crystal X-ray diffraction. The molecular modelling studies also corroborated the biological activity of the compounds. Further, in silico findings revealed that all these tested compounds exhibited good ADME properties and drug likeness and thus may be considered as potential candidates for further drug development. Graphic abstract: [Figure not available: see fulltext.]
Design, synthesis, and evaluation of novel diphenyl ether derivatives against drug-susceptible and drug-resistant strains of?Mycobacterium tuberculosis
Kar, Sidhartha S.,Bhat, Varadaraj G.,Shenoy, Vishnu P.,Bairy, Indira,Shenoy, G. Gautham
, p. 60 - 66 (2018/12/05)
In our efforts to develop druggable diphenyl ethers as potential antitubercular agents, a series of novel diphenyl ether derivatives (5a–f, 6a–f) were designed and synthesized. The representative compounds showed promising in vitro activity against drug-susceptible, isoniazid-resistant, and multidrug-resistant strains of Mycobacterium tuberculosis with MIC values of 1.56?μg/ml (6b), 6.25?μg/ml (6a–d), and 3.125?μg/ml (6b–c), respectively. All the synthesized compounds exhibited satisfactory safety profile (CC50?>?300?μg/ml) against Vero and HepG2 cells. Reverse phase HPLC method was used to probe the physicochemical properties of the synthesized compounds. This series of compounds demonstrated comparatively low logP values. pKa values of representative compounds indicated that they were weak acids. Additionally, in vitro human liver microsomal stability assay confirmed that the synthesized compounds possessed acceptable stability under study conditions. The present study thus establishes compound 6b as the most promising antitubercular agent with acceptable drug-likeness.
Rational design and synthesis of novel diphenyl ether derivatives as antitubercular agents
Kar, Sidhartha S.,Bhat, Varadaraj,Rao, Praveen P. N.,Shenoy, Vishnu P.,Bairy, Indira,Shenoy, G. Gautham
, p. 2299 - 2310 (2016/07/26)
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.
A route to the structure proposed for puetuberosanol and approaches to the natural products marshrin and phebalosin
Gillmore, Adam,Lauret, Christelle,Roberts, Stanley M.
, p. 4363 - 4375 (2007/10/03)
Synthesis of the structure claimed for puetuberosanol 1 (using the Juliá-Colonna oxidation in a key step) showed that the natural product was a different material. The isomeric epoxy alcohols 16-18 can be discounted from the alternatives. An analogue 19 of marshrin 2 was prepared but the synthesis of the natural product was thwarted by failure of a Juliá-Colonna oxidation in the key step. The epoxy ketone 29 was prepared by Darzens condensation and was converted into (±)-phebalosin 3.
Carboxy-substituted cinnamides: A novel series of potent, orally active LTB4 receptor antagonists
Greenspan, Paul D.,Fujimoto, Roger A.,Marshall, Paul J.,Raychaudhuri, Anil,Lipson, Kenneth E.,Zhou, Huanghai,Doti, Robert A.,Coppa, David E.,Zhu, Lijuan,Pelletier, Roberta,Uziel-Fusi, Susan,Jackson, Robert H.,Chin, Michael H.,Kotyuk, Bernard L.,Fitt, John J.
, p. 164 - 172 (2007/10/03)
A series of carboxy-substituted cinnamides were investigated as antagonists of the human cell surface leukotriene B4 (LTB4) receptor. Binding was determined through measurement of [3H]-LTB4 displacement from hum
