New Pyrano‐4H‐benzo[g]chromene‐5,10‐diones with Antiparasitic and Antioxidant Activities

Abstract

New pyranonaphthoquinone derivatives were synthesized and investigated for their activity against Trypanosoma brucei, Leishmania major, and Toxoplasma gondii parasites. The pentafluorophenyl derivative was efficacious against T. brucei with single digit micromolar EC 50 values and against T. gondii with even submicromolar values. The 3-chloro-4,5-dimethoxyphenyl derivative showed an activity against amastigotes of Leishmania major parasites comparable to that of amphotericin B. In addition, antioxidant activities were observed for the bromophenyl derivatives, and their redox behavior was studied by cyclovoltammetry. Antiparasitic and antioxidative activities of the new naphthoquinone derivatives appear uncorrelated.

Synthesis and Evaluation of Some New 4H-Pyran Derivatives as Antioxidant, Antibacterial and Anti-HCT-116 Cells of CRC, with Molecular Docking, Antiproliferative, Apoptotic and ADME Investigations

“…Animal model studies and molecular analyses of human tumors have indicated that many of these regulators are altered in cancer, particularly, CDK4, CDK6 and CDK2 and their substrates, which control progression through the G1/S phases of cell-cycle division. A literature survey confirmed that CKD2 is a valid target for 4 H -pyran derivatives ( Figure 2 ) with anticancer activities [ 33 , 34 , 35 , 36 , 37 ]. Therefore, to investigate whether or not the cellular mechanism by which the most active cytotoxic derivatives 4d and 4k suppressed the proliferation of HCT-116 cells is related to the inhibition of CDK2, the induced-fit docking approach in the ATP active site of the enzyme using the Glide program of Schrodinger-Maestro 11.2 was employed prior to the in vitro inhibitory kinase assays.…”

“… Examples of pyran-containing compounds with antibacterial [ 33 ], antioxidant [ 34 ] and anticancer activities via inhibition of CDK2 [ 35 , 36 , 37 ]. …”

“…Consequently, in a quest to design new chemical compounds to meet all these health needs, the pyran scaffold can be considered a potential synthetic target. The 4 H -Pyran motif is embedded in bioactive 4 H -chromene derivatives which display antitumoral and antibacterial effects, such as compounds Ia , b [ 33 ], and antioxidant activities, such as derivatives IIa , b [ 34 ]. Moreover, compelling evidence has indicated that CDK2 is a valid anticancer target of pyran-containing compounds III – VI , as shown in Figure 2 [ 35 , 36 , 37 ], due to its pro-tumorigenic role via interference with cell division cycle.…”

The Relevance and Insights on 1,4-Naphthoquinones as Antimicrobial and Antitumoral Molecules: A Systematic Review

“…In addition, lawsone has been used to prepare naphtho[2,3-b]furan-4,9-dione derivatives via transition metal-free tandem formal [3+2] by a base-promoted alkynylation and subsequent intramolecular addition reaction with aryl bromoacetylenes [50]. The synthesis of pyranonaphthoquinone derivatives has been reported in a multi-component one-pot reaction by a Knoevenagel reaction of malononitrile and aryl aldehydes followed by Michael addition of lawsone (Figure 9) [54]. Moreover, novel podophyllotoxin-naphthoquinone derivatives using microwave-assisted three-component reactions have been reported.…”

The Current Directions of Searching for Antiparasitic Drugs

“…The pentafluorophenyl derivative (Figure 7) showed activity against Toxoplasma gondii. In turn, a derivative of 3-chloro-4,5-dimethoxyphenyl, comparable to amphotericin B, turned out to be effective in the control of Leishmania major but it was also quite toxic to Vero cells [54]. The growing resistance and toxicity of current drugs are forcing researchers to seek alternative treatment options.…”