curcumin and kojic-acid

The Hippo signaling pathway extorts several signals that concomitantly target the activity of transcriptional cofactor yes associated protein (YAP). YAP is a key regulator that elicits signature gene expression by coupling with transcriptional enhanced associate domain (TEAD) family of transcriptional factors. The YAP-TEAD complex via target gene expression gets associated with the development, proliferation, and progression of cancerous cells. Moreover, YAP adorns cells with several oncogenic traits such as inhibition of apoptosis, enhanced proliferation, drug resistance, and immune response suppression, which later became associated with various diseases, particularly cancer. Therefore, inhibition of the YAP activity is an appealing and viable therapeutic target for cancer treatment. This review highlights the recent advances in existing and novel synthetic therapeutics targeting YAP inhibition and regulation. The synthetically produced YAP

Topics: Animals; Antineoplastic Agents; Curcumin; Humans; Molecular Targeted Therapy; Niflumic Acid; Oxadiazoles; Pyrones; TEA Domain Transcription Factors; Triazines; Verteporfin; YAP-Signaling Proteins; Zoledronic Acid

Synthesis and biological evaluation of unsymmetrical curcumin analogues (UCAs) have been achieved. Tyrosinase inhibitory activities were found for most of the prepared synthetic UCAs. Among them, compounds containing 4-hydroxyl-substituted phenolic rings with C-2/C-4- or C-3/C-4-dihydroxyl-substituted diphenolic rings were more active (IC(50) = 1.74~16.74 μM) than 4-butylresorcinol and kojic acid, which suggested that the 4-hydroxyl groups in UCAs play a crucial role in tyrosinase inhibitory activities. The inhibition kinetics analyzed by Lineweaver-Burk plots revealed compounds 3c and 3i containing catecholic rings were mixed-competitive inhibitors, whereas compounds 3d and 3j containing resorcinolic rings were competitive inhibitors. The preliminary evaluation results of acute toxicity showed the representative 3d and 3j were non-toxic in mice dosed at 1,200 mg/kg. This research suggests that, with the advantage of being readily prepared small molecules, polyphenolic UCAs have the potential to develop into pharmacological inhibitors of tyrosinase.

Topics: Animals; Curcumin; Female; Inhibitory Concentration 50; Kinetics; Male; Mice; Mice, Inbred Strains; Monophenol Monooxygenase; Polyphenols; Pyrones; Resorcinols; Toxicity Tests, Acute

Sixteen novel compounds; 3alpha-methoxyserrat-14-en-21beta-ol (1) and 3beta-methoxyserrat-14-en-21beta-ol (2) and their curcumin, kojic acid, quercetin, and baicalein conjugates (3)-(18) were designed, synthesized, and evaluated for in vitro anti-HIV-1 reverse transcriptase (RT) activity in infected C8166-CCR5 cells, a human CD4(+) T-lymphocyte cell line. Among them, kojic acid derivatives, 9-12 showed significant biological activity. In particular, the compound 13, the conjugate of two molecules of 3alpha-methoxyserrat-14-en-21beta-ol (1) and one molecule of kojic acid, exerted significant anti-HIV activity with an EC50 value of 0.12microg/mL.

Topics: Antiviral Agents; Cell Line; Cell Survival; Curcumin; Flavanones; HIV Infections; HIV-1; Humans; Molecular Structure; Pyrones; Quercetin; Reverse Transcriptase Inhibitors; RNA-Directed DNA Polymerase; T-Lymphocytes; Triterpenes; Viral Proteins