Inhibitory Effect of Chlorogenic Acid Analogues Comprising Pyridine and Pyrimidine on α-MSH-Stimulated Melanogenesis and Stability of Acyl Analogues in Methanol

• Published in: Pharmaceuticals (Basel, Switzerland) Vol. 14; no. 11; p. 1176
• Main Authors: Sim, Jaeuk, Lanka, Srinu, Jo, Jeong-Woong, Chaudhary, Chhabi Lal, Vishwanath, Manjunatha, Jung, Chan-Hyun, Lee, Young-Hee, Kim, Eun-Yeong, Kim, Young-Soo, Hyun, Soon-Sil, Lee, Hee-Soon, Lee, Kiho, Seo, Seung-Yong, Viji, Mayavan, Jung, Jae-Kyung
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 17.11.2021; MDPI
• Subjects: Apoptosis; B16 melanoma cells; Bone cancer; Chemistry; chlorogenic acid; Communication; Melanoma; Pharmaceutical sciences; pyridine; pyrimidine; α-MSH-stimulated melanogenesis; pyridine; B16 melanoma cells; pyrimidine; chlorogenic acid; α-MSH-stimulated melanogenesis
• ISSN: 1424-8247; 1424-8247
• DOI: 10.3390/ph14111176

In continuation of studies for α-MSH stimulated melanogenesis inhibitors, we have evaluated the design, synthesis, and activity of a new series of chlorogenic acid (CGA) analogues comprising pyridine, pyrimidine, and diacyl derivatives. Among nineteen synthesized compounds, most of them (fifteen) exhibited better inhibitions of melanin formation in B16 melanoma cells. The results illustrated that a pyridine analogue and a diacyl derivative of CGA showed superior inhibition profiles (IC : 2.5 ± 0.7 μM and 1.1 ± 0.1 μM, respectively) of -MSH activities than positive controls, kojic acid and arbutin (IC : 54 ± 1.5 μM and 380 ± 9.5 μM, respectively). The SAR studies showed that both -CF and -Cl groups exhibited better inhibition at the position on benzylamine than their and positions. In addition, the stability of diacyl analogues of CGA in methanol monitored by HPLC for 28 days indicated the steric bulkiness of acyl substituents as a key factor in their stability.