ABSTRACT
UV irradiation induced formation of reactive oxygen radical species and matrix metalloproteinases (MMPs) are thought to be involved in photo-damage to the skin. MMP-1 is the major collagenolytic enzyme responsible for collagen destruction in skin tissue. To develop new anti-photoaging agents, a series of 2,2'-dithiocinnamate derivatives and 2,2'-dithio or 2-thiobenzoate derivatives were designed and synthesized. The biological activities of the synthesized compounds were assayed for ABTS [2,2'-azinobis-(3-ethyl-benzo-thiazoline-6-sulfonic acid)] radical scavenging activity, MMP-1 inhibitory activity, and cytotoxicity to human dermal fibroblast cells. Compounds with potential of resistance to UV irradiation were identified. These compounds are expected to be useful for preventing photo-damage to the skin.
Subject(s)
Cinnamates/chemistry , Cinnamates/pharmacology , Free Radical Scavengers/chemical synthesis , Free Radical Scavengers/pharmacology , Matrix Metalloproteinase Inhibitors , Protease Inhibitors/chemical synthesis , Protease Inhibitors/pharmacology , Radiation-Protective Agents/chemical synthesis , Radiation-Protective Agents/pharmacology , Salicylates/chemical synthesis , Salicylates/pharmacology , Skin Aging/drug effects , Sulfur/chemistry , Benzothiazoles/chemistry , Caseins/chemistry , Cell Survival/drug effects , Collagen/chemistry , Collagen/radiation effects , Fibroblasts/drug effects , Humans , Indicators and Reagents , Skin/chemistry , Skin/drug effects , Skin/radiation effects , Sulfonic Acids/chemistry , Ultraviolet RaysABSTRACT
Present studies were undertaken on the preparation of synthetic analogues of bis- or tetra-coumarins and their activity against HIV-1 integrase (HIV-1 IN). Among these coumarin analogues, compounds 14, 16 and 18 were found to be potent molecules against HIV-1 IN at IC50 values of 0.96, 0.58, and 0.49 microM, respectively. The results provided a tool for guiding the further design of more potent antiviral agents and for predicting the affinity of related compounds.
Subject(s)
Coumarins/chemical synthesis , Coumarins/pharmacology , HIV Integrase Inhibitors/chemical synthesis , HIV Integrase Inhibitors/pharmacology , HIV-1/drug effects , HIV-1/enzymology , Chemical Phenomena , Chemistry, Physical , HIV Integrase/metabolism , Magnetic Resonance Spectroscopy , Mass Spectrometry , Oligonucleotides/chemical synthesis , Oligonucleotides/pharmacology , Spectrophotometry, InfraredABSTRACT
Nineteen biscoumarins bearing free and modified hydroxyl substituents at benzoyloxyphenyl linker have been synthesized by multiple step synthesis. Among these biscoumarins, thirteen were found to be active molecules against HIV-1 integrase (HIV-1 IN). The structure-activity relationship of the nineteen compounds on HIV IN may be useful for the design of potent therapeutic agents.
Subject(s)
Coumarins/chemical synthesis , Coumarins/pharmacology , HIV Integrase Inhibitors/chemical synthesis , HIV Integrase Inhibitors/pharmacology , HIV-1/enzymology , Acetylation , Flavonoids/chemistry , HIV-1/drug effects , Hydrolysis , Hydroxylation , Indicators and Reagents , Magnetic Resonance Spectroscopy , Oligonucleotides/chemical synthesis , Oligonucleotides/pharmacology , Phenols/chemistry , Polyphenols , Spectrometry, Mass, Fast Atom Bombardment , Structure-Activity Relationship , Thioctic Acid/chemistryABSTRACT
Six novel selenium-containing polyphenolic acid esters were synthesized and evaluated as antioxidants and 5-lipoxygenase inhibitors. Synthesis of the title compounds involved the Mitsunobu reaction of polyphenolic acids with 2-phenylselenoethanol. Compounds and were found to be very effective antioxidants and 5-lipoxygenase inhibitors with activity comparable to or better than caffeic acid (3,4-dihydroxycinnamic acid) phenethyl ester (CAPE).