- Novel coupled molecules from active structural motifs of synthetic and natural origin as immunosuppressants
-
Introduction: Nitric oxide (NO) is an important mediator in the pathogenesis and control of immune system-related disorders and its levels are modulated by inducible NO synthase (iNOS). Oxidative stress is another pathological indication in majority of autoimmune disorders. The present study aims at the development of coupled molecules via selection of pharmacophores for both immunomodulatory and antioxidant activities through iNOS inhibition. Methods: Variedly substituted coumarin moieties are coupled with naturally occurring phenols through an amide linkage and were predicted for activities using computer-based program PASS. The compounds predicted to have dual activities were synthesized. Docking studies were carried out against iNOS (PDB 1R35) and compounds having good docking score were evaluated for immunomodulatory and antioxidant activities. Results: The synthesized compounds were found to be pure and were obtained in good yields. Compounds with maximum docking score (YR1a, YR2e, YR2c and YR4e) were selected for evaluation by in vitro models. Compounds YR2e and YR2c markedly inhibited the reduction of NBT dye and showed maximum percent iNOS inhibition. In DPPH assay, compound YR4e was observed as the most potent antioxidant (EC50 0.33 μM/mL). Based on these studies, compounds YR2e and YR2c were selected for haemagglutination test. Compound YR2e was observed as the most active immunosuppressant with maximal inhibitory ability of iNOS and NBT reduction and lower HAT value of 3.5. Conclusion: Compound YR2e can be utilized as a pharmacological agent in the prevention or treatment of immunomodulatory diseases such as tumors, rheumatoid arthritis, ulcerative colitis, organ transplant and other autoimmune disorders.
- Minhas, Richa,Bansal, Gulshan,Bansal, Yogita
-
p. 544 - 554
(2020/06/21)
-
- Synthesis and structural characterization of 2-benzylidenebenzofuran-3-(2 H)-ones
-
Novel aurone derivatives e.g. 2-(2-(3-methylbut-2-enyloxy)benzylidene) benzofuran-3(2H)-one (3a), 2-(2-(allyloxy)benzylidene)-7-methoxybenzofuran-3(2H) -one (3b), and 2-(5-bromo-2-(3-methylbut-2-enyloxy)benzylidene)-6- hydroxybenzofuran-3(2H)-one (3c) were synthesized. All these compounds were characterized by IR, 1H and 13C NMR, and Mass spectroscopy. Finally, the crystal structures were solved by single crystal X-ray diffraction data and the structures were analyzed in terms of supramolecular interactions. [Supplementary materials are available for this article. Go to the publisher's online edition of Molecular Crystals and Liquid Crystals for the following free supplemental resource(s): supplemental figures 1-12; Spectral data (IR, NMR, MS, and HRMS) of the compounds 3a, 3b and 3c are available in the supporting information in.pdf format. Crystallographic information files (.cif) of compounds 3a, 3b, and 3c are available in the electronic format.]
- Rambabu,Srinivas,Manjulatha, Khanapur,Basavoju, Srinivas,Basaveswara Rao,Pal, Manojit
-
-
- Antimalarial activity enhancement in hydroxymethylcarbonyl (HMC) isostere-based dipeptidomimetics targeting malarial aspartic protease plasmepsin
-
Plasmepsin (Plm) is a potential target for new antimalarial drugs, but most reported Plm inhibitors have relatively low antimalarial activities. We synthesized a series of dipeptide-type HIV protease inhibitors, which contain an allophenylnorstatine-dimethylthioproline scaffold to exhibit potent inhibitory activities against Plm II. Their activities against Plasmodium falciparum in the infected erythrocyte assay were largely different from those against the target enzyme. To improve the antimalarial activity of peptidomimetic Plm inhibitors, we attached substituents on a structure of the highly potent Plm inhibitor KNI-10006. Among the derivatives, we identified alkylamino compounds such as 44 (KNI-10283) and 47 (KNI-10538) with more than 15-fold enhanced antimalarial activity, to the sub-micromolar level, maintaining their potent Plm II inhibitory activity and low cytotoxicity. These results suggest that auxiliary substituents on a specific basic group contribute to deliver the inhibitors to the target Plm.
- Hidaka, Koushi,Kimura, Tooru,Ruben, Adam J.,Uemura, Tsuyoshi,Kamiya, Mami,Kiso, Aiko,Okamoto, Tetsuya,Tsuchiya, Yumi,Hayashi, Yoshio,Freire, Ernesto,Kiso, Yoshiaki
-
scheme or table
p. 10049 - 10060
(2009/04/07)
-
- Organotin(benzeneazo)phenoxy Acetates - Examples of Seven-coordinated Triorganotin Chelates
-
Triorganotin derivatives of a number of (benzeneazo) phenoxyacetic acids have been prepared.The derivatives of the tridentate ligands are formulated as six-coordinated organotin complexes on the basis of IR and electronic absorption spectra.Derivatives of
- Sengupta, A,Chattopadhyay, T K,Majee, B
-
p. 1090 - 1095
(2007/10/02)
-