Evaluation of the Inhibitory Effects of Pyridylpyrazole Derivatives on LPS-Induced PGE Productions and Nitric Oxide in Murine RAW 264.7 Macrophages.

A series of thirteen triarylpyrazole analogs were investigated as inhibitors of lipopolysaccharide (LPS)-induced prostaglandin E (PGE) and nitric oxide (NO) production in RAW 264.7 macrophages. The target compounds - have first been assessed for cytotoxicity against RAW 264.

Discovery of New Imidazo[2,1-]thiazole Derivatives as Potent Pan-RAF Inhibitors with Promising and Anti-melanoma Activity.

BRAF is an important component of MAPK cascade. Mutation of BRAF, in particular V600E, leads to hyperactivation of the MAPK pathway and uncontrolled cellular growth. Resistance to selective inhibitors of mutated BRAF is a major obstacle against treatment of many cancer types.

Inhibitory effects of triarylpyrazole derivatives on LPS-induced nitric oxide and PGE productions in murine RAW 264.7 macrophages.

In this article, a series of 22 triarylpyrazole derivatives were evaluated for in vitro antiinflammatory activity as inhibitors of nitric oxide (NO) and prostaglandin E (PGE) release induced by lipopolysaccharide (LPS) in murine RAW 264.7 macrophages. The synthesized compounds 1a-h, 2a-f and 3a-h were first examined for their cytotoxicity for determination of the non-toxic concentration for antiinflammatory screening, so that the inhibitory effects against NO and PGE production were not caused by non-specific cytotoxicity.

Design, synthesis, and anticancer activity of imidazo[2,1-b]oxazole-based RAF kinase inhibitors.

In the present work, a novel series of B-RAF kinase inhibitors having imidazo[2,1-b]oxazole scaffold was designed and synthesized based on the structures of the well-known B-RAF inhibitors. The twenty two final compounds were tested over A375 and SKMEL28 cell lines to determine the primary cytotoxic activity of these compounds, and their activities were compared with that of sorafenib as a standard. Compounds 11c, 11e, 11o, 11q, 11r, and 11u exhibited higher cellular activity compared to sorafenib with IC values of 7.

Design, synthesis, potent antiproliferative activity, and kinase inhibitory effects of new triarylpyrazole derivatives possessing different heterocycle terminal moieties.

A new series of triarylpyrazole derivatives having different heterocycle terminal groups have been designed and synthesised. Compounds - and exhibited the highest mean percentage inhibition against the 58 cancer cell lines at a concentration of 10 μM, and thus were next examined in 5-dose testing mode to detect their IC value. The four compounds showed stronger antiproliferative activities upon comparing their results with sorafenib as a reference compound.

Design, synthesis, in vitro anticancer evaluation, kinase inhibitory effects, and pharmacokinetic profile of new 1,3,4-triarylpyrazole derivatives possessing terminal sulfonamide moiety.

The present work describes the design and synthesis of a novel series of 1,3-diaryl-4-sulfonamidoarylpyrazole derivatives 1a-q and 2a-q and their in vitro biological activities. The target compounds were evaluated for antiproliferative activity against NCI-60 cell line panel. Compounds 1c, 1g, 1k-m, 1o, 2g, 2h, 2k-m, 2o, and 2q showed the highest mean inhibition percentages at 10 µM single-dose testing and were selected to be tested at 5-dose mode.

Synthesis of New Triarylpyrazole Derivatives Possessing Terminal Sulfonamide Moiety and Their Inhibitory Effects on PGE₂ and Nitric Oxide Productions in Lipopolysaccharide-Induced RAW 264.7 Macrophages.

This article describes the design, synthesis, and in vitro anti-inflammatory screening of new triarylpyrazole derivatives. A total of 34 new compounds were synthesized containing a terminal arylsulfonamide moiety and a different linker between the sulfonamide and pyridine ring at position 4 of the pyrazole ring. All the target compounds were tested for both cytotoxicity and nitric oxide (NO) production inhibition in lipopolysaccharide (LPS)-induced RAW 264.

Design and synthesis of new RAF kinase-inhibiting antiproliferative quinoline derivatives. Part 2: Diarylurea derivatives.

This article describes the design, synthesis, and biological screening of a new series of diarylurea derivatives possessing quinoline nucleus. Nine target compounds were selected by the National Cancer Institute (NCI, Bethesda, Maryland, USA) for in vitro antiproliferative screening against a panel of 58 cancer cell lines of nine cancer types. Following one-dose initial screening, compounds 1d-g and 2b were selected for 5-dose screening in order to calculate their IC and total growth inhibition (TGI) values against the cell lines.

Synthesis, in vitro Antiproliferative and Antiinflammatory Activities, and Kinase Inhibitory effects of New 1,3,4-triarylpyrazole Derivatives.

Background: Pyrazole derivatives have been reported as both anticancer and antiinflammatory agents.

Objective: This study was conducted to develop new pyrazole derivatives as potential anticancer and/or antiinflammatory agents. Their molecular mechanisms of action have been investigated.

Design, synthesis, and in vitro antiproliferative and kinase inhibitory effects of pyrimidinylpyrazole derivatives terminating with arylsulfonamido or cyclic sulfamide substituents.

A novel series of substituted pyrimidine compounds bearing N-phenylpyrazole and terminating with aryl and cyclic sulfonamido moiety were designed, synthesized, and evaluated in vitro as antiproliferative agents against a panel of 53 cell lines of different tissues at the NCI. Among them, compound 1d with p-chlorobenzenesulfonamido terminal moiety, ethylene spacer, and 4-chloro-3-methoxyphenyl ring at position 3 of the pyrazole nucleus showed the highest mean percentage inhibition value over the whole cancer cell line panel at 10 μM concentration. It showed broad-spectrum antiproliferative activity over many cell lines of different cancer types.

Design, synthesis, broad-spectrum antiproliferative activity, and kinase inhibitory effect of triarylpyrazole derivatives possessing arylamides or arylureas moieties.

A novel series of 1,3,4-triarylpyrazole derivatives possessing terminal arylamide or arylurea terminal moieties has been designed and synthesized. Their in vitro antiproliferative activities were investigated against a panel of 58 cell lines of nine different cancer types at the NCI, USA. The urea analogues 2b, 2c, and 2f as well as the amide derivatives 3e and 3f exerted the highest mean % inhibition values over the 58 cell line panel at 10 μM, and thus were further tested in 5-dose testing mode to determine their GI50, TGI, and LC50 values.

Design, synthesis, in vitro antiproliferative evaluation, and kinase inhibitory effects of a new series of imidazo[2,1-b]thiazole derivatives.

Design and synthesis of a new series of 5,6-diarylimidazo[2,1-b]thiazole derivatives possessing terminal aryl sulfonamide moiety are described. Their in vitro antiproliferative activities against a panel of 57 human cancer cell lines of nine different cancer types were tested at the NCI. Compounds 8a, 8b, 8n, 8q, 8t, and 8u showed the highest mean % inhibition values over the 57 cell line panel at 10 μM, and they were further tested in 5-dose testing mode to determine their IC50 values.

Synthesis and broad-spectrum antiproliferative activity of diarylamides and diarylureas possessing 1,3,4-oxadiazole derivatives.

A series of diarylamides and diarylureas possessing 1,3,4-oxadiazole scaffold was designed and synthesized. Their in vitro antiproliferative activities were tested against a panel of 58 cell lines of nine different cancer types at the NCI, and compared with Sorafenib as a reference compound. Most of the compounds showed strong and broad-spectrum antiproliferative activities.

Synthesis and in vitro antiproliferative activity of new 1,3,4-oxadiazole derivatives possessing sulfonamide moiety.

Synthesis of a new series of 1,3,4-oxadiazole derivatives possessing sulfonamide moiety is described. Their in vitro antiproliferative activities against NCI-58 human cancer cell lines of nine different cancer types were tested. Compound 1k with p-methoxybenzenesulfonamido moiety showed the highest mean %inhibition value over the 58 cell line panel at 10 μM concentration.

A new series of diarylamides possessing quinoline nucleus: Synthesis, in vitro anticancer activities, and kinase inhibitory effect.

Synthesis of a new series of diarylamides possessing 6,7-dimethoxy(dihydroxy)quinoline scaffold is described. Their in vitro antiproliferative activities against NCI-58 human cancer cell lines of nine different cancer types were tested. Compounds 1a and 1d-g showed the highest mean %inhibition values over the 58 cell line panel at 10 μM, and they were further tested in 5-dose testing mode to determine their IC50 values.

Cell-based biological evaluation of a new bisamide FMS kinase inhibitor possessing pyrrolo[3,2-c]pyridine scaffold.

A bisamide compound 1 possessing the pyrrolo[3,2-c]pyridine nucleus was synthesized and biologically evaluated. It was tested for kinase inhibitory activity over a panel of 47 kinases, and its selectivity toward the FMS kinase was accidentally discovered. Compound 1 was tested over a panel of seven ovarian, two prostate, and six breast cancer cell lines at a single dose concentration of 10 µM and showed high activity.