4263-87-0Relevant articles and documents
(±)-trans-2-phenyl-2,3-dihydrobenzofurans as leishmanicidal agents: Synthesis, in vitro evaluation and SAR analysis
Bernal, Freddy A.,Gerhards, Marcel,Kaiser, Marcel,Wünsch, Bernhard,Schmidt, Thomas J.
, (2020/08/06)
Leishmaniasis, a neglected tropical disease caused by parasites of the genus Leishmania, causes a serious burden of disease around the world, represents a threat to the life of millions of people, and therefore is a major public health problem. More effective and non-toxic new treatments are required, especially for visceral leishmaniasis, the most severe form of the disease. On the backdrop that dihydrobenzofurans have previously shown antileishmanial activity, we present here the synthesis of a set of seventy trans-2-phenyl-2,3-dihydrobenzofurans and evaluation of their in vitro activity against Leishmania donovani as well as a discussion of structure-activity relationships. Compounds 8m-o and 8r displayed the highest potency (IC50 4.6). Nonetheless, structural optimization as further requirement was inferred from the high clearance of the most potent compound (8m) observed during determination in vitro of its metabolic stability. On the other hand, chiral separation of 8m and subsequent biological evaluation of its enantiomers demonstrated no effect of chirality on activity and cytotoxicity. Holistic analysis of in silico ADME-like properties and ligand efficiency metrics by a simple scoring function estimating druglikeness highlighted compounds 16c, 18 and 23 as promising candidates for further development. Overall, the potential of trans-2-phenyl-2,3-dihydrobenzofurans as leishmanicidal agents was confirmed.
Low molecular weight lignin suppresses activation of NF-κB and HIV-1 promoter
Mitsuhashi, Shinya,Kishimoto, Takao,Uraki, Yasumitsu,Okamoto, Takashi,Ubukata, Makoto
, p. 2645 - 2650 (2008/12/21)
Human immunodeficiency virus type 1 (HIV-1) is a cytopathic retrovirus and the primary etiological agent of acquired immunodeficiency syndrome (AIDS) and related disorders. In cells chronically infected with HIV-1, nuclear factor-κB (NF-κB) activation by external stimuli such as tumor necrosis factor α (TNFα) augments replication of HIV-1. NF-κB involves in many diseases such as inflammation, cancer, and Crohn's disease. In this paper, we exhibit that (i) HIV-1gene expression was inhibited by lignin, (ii) fraction of small molecular mass in HBS lignin (less than 0.5 kDa) had stronger inhibitory effects than large molecular mass (more than 1.3 kDa), (iii) lignin also inhibited activation of NF-κB induced by TNFα, (iv) among six lignin dimer-like compounds, compound 6 containing β-5 bond has more potent inhibitory activity than compounds 1, 2, 3, 4 and 5, which contain β-1, β-O-4, 5-5, or β-β structural units. These results suggested that small molecules of lignin inhibit HIV-1 replication through suppression of HIV-1 transcription from LTR including activation via NF-κB. Low molecular lignin may be a beneficial material or drug leads as a new class for AIDS and NF-κB-related diseases.
LIGNANS IN CELL CULTURES OF PICEA GLEHNII
Nabeta, Kensuke,Hirata, Megumi,Ohki, Yuriko,Samaraweera, S. W.Ananda,Okuyama, Hiroshi
, p. 409 - 414 (2007/10/02)
A suspension culture derived from the seedling leaves of Picea glehnii accumulated two lignans, pinoresinol and trans-dihydrodehydrodiconiferyl alcohol.The enantiomeric compositions of pinoresinol and dihydrodehydrodiconifery
