Natural abenquines and synthetic analogues: Preliminary exploration of their cytotoxic activity

Abstract

In this study, we explore the cytotoxic activity of four natural abenquines (2a-d) and fourteen synthetic analogues (2e-j and 3a-h) against a panel of six human cancer cell lines using a SRB assay. It was found that most of the compounds revealed higher levels of cytotoxic activities than naturally occurring abenquines. The analogues carrying ethylpyrrolidinyl and ethylpyrimidinyl with either an acetyl group (2h-i) or a benzoyl group (3f-g), were the most potent against all human cancer cell lines and displayed EC between a range of 0.6-3.4μM. Notably, of the compounds tested, compound 2i proved the most cytotoxic against both ovarian (A2780) and breast (MCF7) cells, showing EC=0.6 and 0.8μM respectively. Likewise, the analogues 2i, 3f and 3g showed strong activity against cell HT29 with EC=0.9μM for these compounds.

In Vitro and In Silico Study of Analogs of Plant Product Plastoquinone to Be Effective in Colorectal Cancer Treatment

“…Over the last years or so, the use of 1,4-quinone, an important source of natural products, has enabled the design of efficient and active molecules with improved pharmacological properties in the search of new molecules with cytotoxic activity [ 11 , 12 , 13 , 14 , 15 , 16 ]. The 1,4-quinone and 1,4-naphthoquinone moieties are well-represented in bioactive natural structures and their anticancer effects, including anti-colorectal cancer properties, have been documented in several studies.…”

Natural Abenquines and Their Synthetic Analogues Exert Algicidal Activity against Bloom-Forming Cyanobacteria

“…The preparation of analogues (4e−h) involved the reaction of an equivalent amount of the different amines and quinone 3a. 34,40 Further modification on the abenquine structure involved replacement of the acetyl moiety by the bulkier group benzoyl (Figure 2). To obtain the analogues 5a−h, the required intermediate quinone 3b was prepared employing the same chemical procedure used for the synthesis of 3a.…”

“…Initially the amino acid moiety was substituted with different amines, maintaining the acetamide group as part of the abenquine scaffold. The preparation of analogues ( 4e – h ) involved the reaction of an equivalent amount of the different amines and quinone 3a . , …”

Discovery of a new family of heterocyclic amine linked plastoquinone analogs for antimicrobial evaluation

“…The second one is the production of the semiquinones by a one‐electron reduction (Castro, Mariani, Panek, Eleutherio, & Pereira, ; Gutierrez, ; Widhalm & Rhodes, ). Recent years have witnessed respectable progress in the development of biologically active 1,4‐quinones based on natural compounds (Johnson‐Ajinwo et al, ; Nain‐Perez et al, ; Nain‐Perez, Barbosa, Maltha, & Forlani, ). 1,4‐Quinone moiety constitutes the fundamental framework of versatile natural or synthetic quinone molecules such as plastoquinone (PQ) (Kawamukai, ), mitomycin C (Begleiter, ; Sugiura, ), and thymoquinone (Collett et al, ; El‐Dakhakhany, ; Glamoclija et al, ) since they have extensively found ample and numerous applications in the design and synthesis of pharmacologically active agents exhibiting a wide range of biological activities such as anticancer (Wellington, ; Wellington, Kolesnikova, Nyoka, & McGaw, ), antibacterial (Janeczko, Demchuk, Strzelecka, Kubinski, & Maslyk, ; Jordao et al, ), antifungal (Ryu, Oh, Choi, & Kang, ; Shrestha et al, ), anti‐HIV (Alfadhli et al, ; Ilina et al, ), antimalarial (Carneiro et al, ; Pingaew et al, ), antiallergic (Lien, Huang, Teng, Wang, & Kuo, ), antiinflammatory (Tandon, Chhor, Singh, Rai, & Yadav, ), antithrombotic (Jin, Ryu, Moon, Cho, & Yun, ; Yuk et al, ), lipoxy‐genase inhibitory (Richwien & Wurm, ), human monoamine oxidase (MOA) inhibitory (Cerqueira, Netz, Diniz, do Canto, & Follmer, ), and antiplatelet activities (Lien et al, ; Yuk et al, ).…”

“…Abenquines are natural products containing amino acid residues and the first total synthesis of abenquines has been achieved by Nain‐Perez and coworkers (Nain‐Perez, Barbosa, Maltha, & Forlani, ). Nain‐Perez et al have shown abenquines and their analogs’ cytotoxicity activities against six human tumor cell lines and nonmalignant mouse fibroblasts (Nain‐Perez, Barbosa, Rodriguez‐Hernandez, Kramell, et al, ). Additionally, the same group has also used this class of structures as a model for the synthesis of new herbicides targeting photosynthesis (Nain‐Perez, Barbosa, Maltha, Giberti, & Forlani, ).…”