ABSTRACT
As nitrogen-containing five-membered heterocyclic structural units, the substituted pyrazole derivatives have a broad spectrum of pharmacological activities, especially 4,5-dihydro-1H-pyrazoles that also commonly known as 2-pyrazolines. Since 2010, considerable studies have been found that the 2-pyrazoline derivatives possess potent anticancer activities. In the present review, it covers the pyrazoline derivatives reported by literature from 2010 till date (2010-2019). This review aims to establish the relationship between the anticancer activities variation and different substituents introduced into a 2-pyrazoline core, which could provide important pharmacophore clues for the discovery of new anticancer agents containing 2-pyrazoline scaffold.
Subject(s)
Antineoplastic Agents , Antineoplastic Agents/pharmacology , Humans , Structure-Activity RelationshipABSTRACT
BACKGROUND: Almost 50% of metastatic melanomas harbor BRAF mutations. Since 2011, BRAF inhibitors have exhibited striking clinical benefits in BRAF-mutant melanoma patients. Unfortunately, their therapeutic effects are often temporary. The resistance mechanisms vary and can be broadly classified as MAPK reactivation-dependent and -independent. Elucidation of these resistance mechanisms provides new insights into strategies for overcoming resistance. Indeed, several alternative treatment strategies, including changes in the mode of administration, combinations of BRAF and MEK inhibitors, and immunotherapy have been verified as beneficial to BRAF inhibitor-resistant melanoma patients. Prospect: In this review, we discuss promising strategies for overcoming drug resistance and highlighting the prospects for discovering strategies to counteract BRAF inhibitor resistance.
Subject(s)
Antineoplastic Agents/pharmacology , Drug Resistance, Neoplasm/drug effects , Melanoma/therapy , Protein Kinase Inhibitors/pharmacology , Proto-Oncogene Proteins B-raf/antagonists & inhibitors , Skin Neoplasms/therapy , Antineoplastic Agents/chemistry , Humans , Immunotherapy , Melanoma/metabolism , Protein Kinase Inhibitors/chemistry , Proto-Oncogene Proteins B-raf/metabolism , Skin Neoplasms/metabolism , Melanoma, Cutaneous MalignantABSTRACT
A series of novel 4-ferrocenylchroman-2-one derivatives were designed and synthesised to discover potent anti-inflammatory agents for treatment of arthritis. All the target compounds had been screened for their anti-inflammatory activity by evaluating the inhibition effect of LPS-induced NO production in RAW 264.7 macrophages. Among them, 4-ferrocenyl-3,4-dihydro-2H-benzo[g]chromen-2-one (3h) was found to be the most potent compound in inhibiting the productions of NO with low toxicity. This compound also exhibited significant inhibition of the productions of IL-6 and TNF-α in RAW 264.7 macrophages. Preliminary mechanism studies indicated that compound 3h could inhibit the activation of LPS-induced NF-κB and MAPKs signalling pathways. The in vivo anti-inflammatory effect of this compound was determined in the rat adjuvant-induced arthritis model.
