3690-46-8Relevant articles and documents
Pleuromutilin derivative with 1, 3, 4-oxadiazole side chain and preparation and application thereof
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Paragraph 0055-0056; 0070; 0090; 0094; 0095; 0102, (2021/07/24)
The invention belongs to the field of medicinal chemistry, and particularly relates to a pleuromutilin derivative with a 1, 3, 4-oxadiazole side chain and preparation and application thereof The pleuromutilin derivative with the 1, 3, 4-oxadiazole side chain is a compound shown in a formula 2 or a pharmaceutically acceptable salt thereof, and a solvent compound, an enantiomer, a diastereoisomer and a tautomer of the compound shown in the formula 2 or the pharmaceutically acceptable salt thereof or a mixture of the solvent compound, the enantiomer, the diastereoisomer and the tautomer in any proportion, including a racemic mixture. The pleuromutilin derivative has good antibacterial activity, is especially suitable for being used as a novel antibacterial agent for systemic system infection of animals or human beings, and has good water solubility.
Development of Novel (+)-Nootkatone Thioethers Containing 1,3,4-Oxadiazole/Thiadiazole Moieties as Insecticide Candidates against Three Species of Insect Pests
Cheng, Wanqing,Fan, Jiangping,Guo, Yong,Han, Meiyue,Ma, Nannan,Yan, Xiaoting,Yang, Ruige
, p. 15544 - 15553 (2022/01/03)
To improve the insecticidal activity of (+)-nootkatone, a series of 42 (+)-nootkatone thioethers containing 1,3,4-oxadiazole/thiadiazole moieties were prepared to evaluate their insecticidal activities against Mythimna separata Walker, Myzus persicae Sulzer, and Plutella xylostella Linnaeus. Insecticidal evaluation revealed that most of the title derivatives exhibited more potent insecticidal activities than the precursor (+)-nootkatone after the introduction of 1,3,4-oxadiazole/thiadiazole on (+)-nootkatone. Among all of the (+)-nootkatone derivatives, compound 8c (1 mg/mL) exhibited the best growth inhibitory (GI) activity against M. separata with a final corrected mortality rate (CMR) of 71.4%, which was 1.54- and 1.43-fold that of (+)-nootkatone and toosendanin, respectively; 8c also displayed the most potent aphicidal activity against M. persicae with an LD50 value of 0.030 μg/larvae, which was closer to that of the commercial insecticidal etoxazole (0.026 μg/larvae); and 8s showed the best larvicidal activity against P. xylostella with an LC50 value of 0.27 mg/mL, which was 3.37-fold that of toosendanin and slightly higher than that of etoxazole (0.28 mg/mL). Furthermore, the control efficacy of 8s against P. xylostella in the pot experiments under greenhouse conditions was better than that of etoxazole. Structure-activity relationships (SARs) revealed that in most cases, the introduction of 1,3,4-oxadiazole/thiadiazole containing halophenyl groups at the C-13 position of (+)-nootkatone could obtain more active derivatives against M. separata, M. persicae, and P. xylostella than those containing other groups. In addition, toxicity assays indicated that these (+)-nootkatone derivatives had good selectivity to insects over nontarget organisms (normal mammalian NRK-52E cells and C. idella and N. denticulata fries) with relatively low toxicity. Therefore, the above results indicate that these (+)-nootkatone derivatives could be further explored as new lead compounds for the development of potential eco-friendly pesticides.
Design, synthesis, and biological evaluation of new challenging thalidomide analogs as potential anticancer immunomodulatory agents
El-Zahabi, Mohamed Ayman,Sakr, Helmy,El-Adl, Khaled.,Zayed, Mohamed,Abdelraheem, Adel S.,Eissa, Sally I.,Elkady, Hazem,Eissa, Ibrahim H.
, (2020/09/16)
Thalidomide and its analogs are immunomodulatory drugs that inhibit the production of certain inflammatory mediators associated with cancer. In the present work, a new series of thalidomide analogs was designed and synthesized to obtain new effective antitumor immunomodulatory agents. The synthesized compounds were evaluated for their cytotoxic activities against a panel of four cancer cell lines (HepG-2, HCT-116, PC3 and MCF-7). Compounds 33h, 33i, 42f and 42h showed strong potencies against all tested cell lines with IC50 values ranging from 14.63 to 49.90 μM comparable to that of thalidomide (IC50 values ranging from 32.12 to 76.91 μM). The most active compounds were further evaluated for their in vitro immunomodulatory activities via estimation of human tumor necrosis factor alpha (TNF-α), human caspase-8 (CASP8), human vascular endothelial growth factor (VEGF), and nuclear factor kappa-B P65 (NF-κB P65) in HCT-116 cells. Thalidomide was used as a positive control. Compounds 33h and 42f showed a significant reduction in TNF-α. Furthermore, compounds 33i and 42f exhibited significant elevation in CASP8 levels. Compounds 33i and 42f inhibited VEGF. In addition, compound 42f showed significant decrease in levels of NF-κB p65. Moreover, apoptosis and cell cycle tests of the most active compound 42f, were performed. The results indicated that compound 42f significantly induce apoptosis in HCT-116 cells and arrest cell cycle at the G2/M phase.
