Tena Pérez Víctor, Apaza Ticona Luis, Serban Andreea Madalina, Acero Gómez Javier, Rumbero Sánchez Ángel
Department of Organic Chemistry , Faculty of Sciences , University Autónoma of Madrid , Cantoblanco , 28049 Madrid , Spain . Email:
Department of Pharmacology, Pharmacognosy and Botany , Faculty of Pharmacy , University Complutense of Madrid , Ciudad Universitaria s/n , 28040 Madrid , Spain.
RSC Med Chem. 2020 Aug 6;11(10):1196-1209. doi: 10.1039/d0md00208a. eCollection 2020 Oct 1.
Thirty-five macamide analogues were synthesised by modifying the initial molecular structure. The resulting structures were confirmed using NMR and MS. Cytotoxicity and the anti-inflammatory activity of these synthetic macamides were evaluated in the THP-1 cell line. Preliminary biological evaluation indicated that most of these synthetic macamides did not present cytotoxicity (MTT assay) in the tested cell line with respect to the control (actinomycin D). Regarding the anti-inflammatory activity, several analogues had a greater potential for inhibition of TNF-α than natural macamides. Synthetic macamide was the most active (IC = 0.009 ± 0.001 μM) compared to the C87 (control). Through looking at the link between the chemical structure and the activity, our study proves that changes made to natural macamides at the level of the alkyl chain, the benzyl position, the amide bond, and the addition of two methyl groups to the aromatic ring ( position) lead us to obtaining new macamides with greater anti-inflammatory activity.
通过修饰初始分子结构合成了35种马卡酰胺类似物。使用核磁共振（NMR）和质谱（MS）对所得结构进行了确认。在THP-1细胞系中评估了这些合成马卡酰胺的细胞毒性和抗炎活性。初步生物学评估表明，相对于对照（放线菌素D），这些合成马卡酰胺中的大多数在测试细胞系中未表现出细胞毒性（MTT法）。关于抗炎活性，几种类似物比天然马卡酰胺具有更大的抑制肿瘤坏死因子-α（TNF-α）的潜力。与C87（对照）相比，合成马卡酰胺 活性最高（IC = 0.009±0.001μM）。通过研究化学结构与活性之间的联系，我们的研究证明，在烷基链、苄基位置、酰胺键水平对天然马卡酰胺进行的改变，以及在芳环（位置）上添加两个甲基，使我们获得了具有更强抗炎活性的新马卡酰胺。
