Lucas Mariana, Freitas Marisa, Zanchetta Marco, Silva Artur M S, Fernandes Eduarda, Ribeiro Daniela
LAQV, REQUIMTE, Laboratory of Applied Chemistry, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal.
LAQV, REQUIMTE & Department of Chemistry, Campus de Santiago, University of Aveiro, 3810-193 Aveiro, Portugal.
Pharmaceuticals (Basel). 2022 Feb 25;15(3):288. doi: 10.3390/ph15030288.
Neutrophils are polymorphonuclear leukocytes recruited to sites of acute inflammation, in response to pathogen invasion and tissue injury. The modulation of their activity, especially oxidative burst, may be important to control the inflammatory process. 2-Styrylchromones (2-SC) are derived from chromones and despite their recognized multiple biological activities, their anti-inflammatory and antioxidant properties are still poorly explored. Therefore, in this study, 43 structurally related 2-SC were evaluated concerning their effects on freshly isolated human neutrophils’ viability and oxidative burst. The studied 2-SC were divided into eight groups according to their substitution at C-4′ on B-ring (none, -OH, -OCH3, -OBn, -CH3, and -NO2), existence and location of -Cl on B-ring, and presence of -Br at C-3 on C-ring. Overall, most of the studied 2-SC did not affect neutrophils’ viability, at physiological relevant concentrations. The ones belonging to B group were the most effective (IC50 values < 2 μM), and present one -OH group at C-4′ or a catechol group at C-3′ and C-4′ on B-ring. These substituents seem to play an important role in the modulatory activity of human neutrophils’ oxidative burst. These results reinforce the great potential of 2-SC’s scaffold for the development of new anti-inflammatory agents.
中性粒细胞是多形核白细胞，在病原体入侵和组织损伤时被募集到急性炎症部位。调节它们的活性，尤其是氧化爆发，对于控制炎症过程可能很重要。2-苯乙烯基色酮（2-SC）衍生自色酮，尽管它们具有多种已被认可的生物活性，但其抗炎和抗氧化特性仍未得到充分研究。因此，在本研究中，评估了43种结构相关的2-SC对新鲜分离的人中性粒细胞活力和氧化爆发的影响。根据它们在B环上C-4′位的取代情况（无、-OH、-OCH3、-OBn、-CH3和-NO2）、B环上-Cl的存在和位置以及C环上C-3位的-Br的存在，将所研究的2-SC分为八组。总体而言，在生理相关浓度下，大多数所研究的2-SC不影响中性粒细胞的活力。属于B组的化合物最有效（IC50值<2μM），且在B环的C-4′位有一个-OH基团或在C-3′和C-4′位有一个邻苯二酚基团。这些取代基似乎在人中性粒细胞氧化爆发的调节活性中起重要作用。这些结果强化了2-SC骨架在开发新型抗炎剂方面的巨大潜力。
