Direct Synthesis of 2‐Acyl Acridines Using Aldimines and Anthranils: Evaluation of Cytotoxicity and Anti‐Inflammatory Activity

Abstract

Rhodium (III)‐catalyzed C−H aminations of aldimines with anthranils followed by intramolecular cyclization are described. These transformations facilitate the efficient generation of 2‐acyl acridines, which are important motifs found in bioactive natural products and pharmaceuticals. All synthesized 2‐acyl acridines were first screened for cytotoxic activity against human renal carcinoma cells (CAKI‐1 and 786‐O) and human breast carcinoma cells (MCF‐7). Compound 3 z showed the most potent cytotoxic activity, which is stronger than that of doxorubicin against CAKI‐1 and 786‐O cells. In addition, compounds that exhibited potent cytotoxicities were selected for further in vitro anti‐inflammatory activity testing using interleukin‐6 (IL‐6) with lipopolysaccharide (LPS)‐induced RAW264.7 cells. Notably, compounds (3 k, 3 n, 3 s and 3 x–3 z) were found to exhibit inhibitory activities that are about two‐ to three‐times more potent than that of the anti‐inflammatory drug dexamethasone.

Sc(OTf)3-Catalyzed Chemodivergent Annulations of γ-Butyrolactone-Fused Cyclopropanes with Anthranils

“…All reactions between the γ-butyrolactone-fused cyclopropanes with anthranils were carried out with flame-dried Schlenk-type glassware using a Schlenk line. The γ-butyrolactone-fused cyclopropanes were prepared as previously described; the substituted anthranils 2b–2l , 2o, and 2n were prepared following literature methods . All other reagents were purchased from commercial suppliers and purified by standard techniques.…”

Analysis of alkaloids (indole alkaloids, isoquinoline alkaloids, tropane alkaloids)

“…Plant secondary metabolites are a diverse range of biologically active molecules having multiple pharmacological actions like antimicrobial, stimulant, analgesic, anthelmintic, anticoagulant, antiacne, and antioxidant, among others (Debnath et al, 2012;Bhakta, 2012, 2013;Dey et al, 2012bDey et al, , 2014Karuna et al, 2018aKaruna et al, , 2018bKundu et al, 2019). Different synthetic compounds show potential biological activity in vitro as well as in vivo ( Jeon et al, 2017;Jeong et al, 2017a, b;Kim et al, 2018;Lee et al, 2018Lee et al, , 2019Richa et al, 2019;Tae et al, 2018), and various formulations of existing drugs are also developed to increase the safety profile (Gorain et al, 2014;Karmakar et al, 2015;Maity et al, 2016). In spite of this technological development, humans from almost every culture are efficiently employing the plant-derived compounds for the anticipation and management of multiple health disorders for many centuries (Dey et al, 2012a, c).…”

Anthranils: versatile building blocks in the construction of C–N bonds and N-heterocycles

“…Later, by using sulfonimide as the directing group, they also completed the synthesis of 2-acyl acridines from aldimines and anthranils. 24 Very recently, Cui et al disclosed a Rh(III)-catalysed C-H amination and cascade annulation reaction for the synthesis of benzimidazole derivatives (Scheme 17). 25 In this protocol, imidamide acted as the directing group and enabled further intramolecular annulation to construct the benzimidazoles.…”