70110-38-2Relevant academic research and scientific papers
Design, synthesis and biological evaluation of novel Pseudomonas aeruginosa DNA gyrase B inhibitors
Balraju, Vadla,Jogula, Sridhar,Krishna, Vagolu Siva,Meda, Nikhila,Sriram, Dharmarajan
, (2020/05/08)
In the present study, we attempted to develop a novel class of compounds active against Pseudomonas aeruginosa (Pa) by exploring the pharmaceutically well exploited enzyme targets. Since, lack of Pa gyrase B crystal structures, Thermus thermophilus gyrase B in complex with novobiocin (1KIJ) was used as template to generate model structure by performing homology modeling. Further the best model was validated and used for high-throughput virtual screening, docking and dynamics simulations using the in-house database for identification of Pa DNA gyrase B inhibitors. This study led to an identification of three lead molecules with IC50 values in range of 6.25–15.6 μM against Pa gyrase supercoiling assay. Lead-1 optimization and expansion resulted in 15 compounds. Among the synthesized compounds six compounds were shown good enzyme inhibition than Lead-1 (IC50 6.25 μM). Compound 13 emerged as the most potential compound exhibiting inhibition of Pa gyrase supercoiling with an IC50 of 2.2 μM; and in-vitro Pa activity with MIC of 8 μg/mL in presence of efflux pump inhibitor; hence could be further developed as novel inhibitor for Pa gyrase B.
MODIFIED PEPTOIDS
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Page/Page column 35, (2018/11/22)
Peptoids are described herein, as well as compositions comprising an aqueous liquid and a peptoid soluble in the aqueous liquid. The peptoids comprise a plurality of N-substituted glycine residues and/or N-substituted β-alanine residues, and at least one heteroalicyclic residue having a general formula (I) wherein W, X, Y1, Y2, Z1 and Z2 are as defined herein.
Salicylic acid based small molecule inhibitor for the oncogenic src homology-2 domain containing protein tyrosine phosphatase-2 (SHP2)
Zhang, Xian,He, Yantao,Liu, Sijiu,Yu, Zhihong,Jiang, Zhong-Xing,Yang, Zhenyun,Dong, Yuanshu,Nabinger, Sarah C.,Wu, Li,Gunawan, Andrea M.,Wang, Lina,Chan, Rebecca J.,Zhang, Zhong-Yin
experimental part, p. 2482 - 2493 (2010/09/03)
The Src homology-2 domain containing protein tyrosine phosphatase-2 (SHP2) plays a pivotal role in growth factor and cytokine signaling. Gain-of-function SHP2 mutations are associated with Noonan syndrome, various kinds of leukemias, and solid tumors. Thus, there is considerable interest in SHP2 as a potential target for anticancer and antileukemia therapy. We report a salicylic acid based combinatorial library approach aimed at binding both active site and unique nearby subpockets for enhanced affinity and selectivity. Screening of the library led to the identification of a SHP2 inhibitor II-B08 (compound 9) with highly efficacious cellular activity. Compound 9 blocks growth factor stimulated ERK1/2 activation and hematopoietic progenitor proliferation, providing supporting evidence that chemical inhibition of SHP2 may be therapeutically useful for anticancer and antileukemia treatment. X-ray crystallographic analysis of the structure of SHP2 in complex with 9 reveals molecular determinants that can be exploited for the acquisition of more potent and selective SHP2 inhibitors.
Targeting mycobacterium protein tyrosine phosphatase B for antituberculosis agents
Zhou, Bo,He, Yantao,Zhang, Xian,Xu, Jie,Luo, Yong,Wang, Yuehong,Franzblau, Scott G.,Yang, Zhenyun,Chan, Rebecca J.,Liu, Yan,Zheng, Jianyu,Zhang, Zhong-Yin
scheme or table, p. 4573 - 4578 (2010/10/03)
Protein tyrosine phosphatases are often exploited and subverted by pathogenic bacteria to cause human diseases. The tyrosine phosphatase mPTPB from Mycobacterium tuberculosis is an essential virulence factor that is secreted by the bacterium into the cytoplasm of macrophages, where it mediates mycobacterial survival in the host. Consequently, there is considerable interest in understanding the mechanism by which mPTPB evades the host immune responses, and in developing potent and selective mPTPB inhibitors as unique antituberculosis (antiTB) agents. We uncovered that mPTPB subverts the innate immune responses by blocking the ERK1/2 and p38 mediated IL-6 production and promoting host cell survival by activating the Akt pathway. We identified a potent and selective mPTPB inhibitor I-A09 with highly efficacious cellular activity, from a combinatorial library of bidentate benzofuran salicylic acid derivatives assembled by click chemistry. We demonstrated that inhibition of mPTPB with I-A09 in macrophages reverses the altered host immune responses induced by the bacterial phosphatase and prevents TB growth in host cells. The results provide the necessary proof-of-principle data to support the notion that specific inhibitors of the mPTPB may serve as effective antiTB therapeutics.
Selective synthesis of isoquinolin-3-one derivatives combining Pd-catalysed aromatic alkylation/vinylation with addition reactions: The beneficial effect of water
Ferraccioli, Raffaella,Forni, Alessandra
experimental part, p. 3161 - 3166 (2009/12/07)
The three-component, palladium/norbornene-catalysed reaction of 1, haloamides 2 and properly substituted olefins 3 performed in DMF/water at: 80 °C selectively gave 5 and 6 through three- and. four-bond-forming reactions, respec tively. The presence of water was crucial to obtain products in fair to good yields,
