Synthesis of N-(3-arylprop-2-ynyl)substituted olanzapine derivatives as potential inhibitors of PDE4B

The linkage between dopamine D2 receptors and PDE activity via cAMP prompted us to design a series of novel N-(3-arylprop-2-ynyl)substituted olanzapine derivatives as potential inhibitors of PDE4B. The target compounds were conveniently prepared by using a simple and inexpensive method involving Pd/C-mediated CC bond forming reaction under Sonogashira conditions. A number of compounds were synthesized by using this strategy in good yields. Some of the compounds showed promising inhibition of PDE4B when tested in vitro that was supported by the docking studies

Synthesis and evaluation of 3-amino/guanidine substituted phenyl oxazoles as a novel class of LSD1 inhibitors with anti-proliferative properties

A series of functionalized phenyl oxazole derivatives was designed, synthesized and screened in vitro for their activities against LSD1 and for effects on viability of cervical and breast cancer cells, and in vivo for effects using zebrafish embryos. These compounds are likely to act via multiple epigenetic mechanisms specific to cancer cells including LSD1 inhibition

12. Le figure di Santi nella chiesa di San Salvatore de Militiis

scheda epigrafica in La pittura medievale a Roma 312-1431, Corpus e Atlante, IV vol., Riforma e Tradizione, a cura di S. Romano, Milano, Jaca Book, 200

Synthesis, anti-inflammatory, analgesic, COX1/2-inhibitory activity, and molecular docking studies of hybrid pyrazole analogues

This article reports on the design, synthesis, and pharmacological activity of a new series of hybrid pyrazole analogues: 5a-5u. Among the series 5a-5u, the compounds 5u and 5s exhibited potent anti-inflammatory activity of 80.63% and 78.09% and inhibition of 80.87% and 76.56% compared with the standard drug ibuprofen, which showed 81.32% and 79.23% inhibition after 3 and 4 hours, respectively. On the basis of in vivo studies, 12 compounds were selected for assessment of their in vitro inhibitory action against COX1/2 and TNF alpha. The compounds 5u and 5s showed high COX2-inhibitory activity, with half-maximal inhibitory concentrations of 1.79 and 2.51 mu M and selectivity index values of 72.73 and 65.75, respectively, comparable to celecoxib (selectivity index = 78.06). These selected compounds were also tested for TNF alpha, cytotoxicity, and ulcerogenicity. Docking studies were also carried out to determine possible interactions of the potent compounds (\(5u and 5s), which also showed high docking scores of -12.907 and -12.24 compared to celecoxib, with a -9.924 docking score. These selective COX2 inhibitors were docked into the active site of COX2, and showed the same orientation and binding mode to that of celecoxib (\(selective COX2 inhibitor). Docking studies also showed that the SO2NH2 of 5u and 5s is inserted deep inside the selective pocket of the COX2-active site and formed a hydrogen-bond interaction with His90, Arg513, Phe518, Ser353, Gln192, and Ile517, which was further validated by superimposed docked pose with celecoxib

Macrocyclic toolbox from epothilone fragment identifies a compound showing molecular interactions with actin and novel promoters of apoptosis in patient-derived brain tumor cells

A simple, practical stereoselective synthesis of the epothilone fragment is developed to obtain a diverse set of expanded 18-membered macrocyclic compounds. These macrocycles contain the C5–C8 sub-unit of epothilone and an additional amino acid moiety incorporated in the 18-membered macrocycle, which allows the synthesis of several analogs with a variation in the chiral side chain. The epothilone fragment was obtained by using an enantiopure epoxide, which was subjected to a regioselective opening, giving the key derivative. Finally, the synthesis of the 18-membered macrocyclic ring was achieved by employing two key steps: (i) acylation with an N-allylated amino acid moiety, and (ii) a ring-closing metathesis (RCM) approach. Computational studies of the macrocyclic compounds obtained from this study with actin give rise to the proposed molecular interactions with the target protein. Further, the screening of our chemical toolbox from this program (i.e., the final products and several intermediates) identified several compounds as promoters of apoptosis in patient-derived brain tumor glioma cells

Cu-mediated 1,3-dipolar cycloaddition of azomethine ylides with dipolarophiles: a faster access to spirooxindoles of potential pharmacological interest

CuI facilitated three-component reaction of isatin derivatives, l-proline and terminal alkynes containing an amide or ester functional group. The multi-component reaction (MCR) afforded a faster and practical synthesis of spirooxindole derivatives. A range of novel spirooxindoles were synthesized by using this straightforward and one-pot efficient methodology. A representative compound showed significant inhibition of PDE4B enzyme in vitro and good interactions with this protein in silico

Synthesis of some coumarinyl chalcones and their antiproliferative activity against breast cancer cell lines

A series of coumarinyl chalcones derivatives were synthesized and evaluated for their antiproliferative activities on three different breast cancer cell lines (MDA-MB231, MDA-MB468, MCF7) and one non-cancer breast epithelial cell line (184B5). The coumarinyl derivatives exhibited anticancer activity against breast cancer cell lines at a micromolar range. A structure-activity relationship (SAR) analysis was performed by studying the effect of substituents on their antiproliferative activities. One of the compound 3i bearing methoxy substitutions at the R1, R2 and R3 positions of the phenyl ring showed comparable potency to the reference drug cisplatin as well as a two-fold higher selectivity for the breast cancer cell lines than 184B5 cells