Synthesis and Evaluation of Antimicrobial and Cytotoxic Activity of Oxathiine-Fused Quinone-Thioglucoside Conjugates of Substituted 1,4-Naphthoquinones

Abstract

A series of new tetracyclic oxathiine-fused quinone-thioglycoside conjugates based on biologically active 1,4-naphthoquinones and 1-mercapto derivatives of per-O-acetyl d-glucose, d-galactose, d-xylose, and l-arabinose have been synthesized, characterized, and evaluated for their cytotoxic and antimicrobial activities. Six tetracyclic conjugates bearing a hydroxyl group in naphthoquinone core showed high cytotoxic activity with EC50 values in the range of 0.3 to 0.9 μM for various types of cancer and normal cells and no hemolytic activity up to 25 μM. The antimicrobial activity of conjugates was screened against Gram-positive bacteria (Staphylococcus aureus, Bacillus cereus), Gram-negative bacteria (Pseudomonas aeruginosa and Escherichia coli), and fungus Candida albicans by the agar diffusion method. The most effective juglone conjugates with d-xylose or l-arabinose moiety and hydroxyl group at C-7 position of naphthoquinone core at concentration 10 µg/well showed antimicrobial activity comparable with antibiotics vancomicin and gentamicin against Gram-positive bacteria strains. In liquid media, juglone-arabinosidic tetracycles showed highest activity with MIC 6.25 µM. Thus, a positive effect of heterocyclization with mercaptosugars on cytotoxic and antimicrobial activity for group of 1,4-naphthoquinones was shown.

Marine Fungal Cerebroside Flavuside B Protects HaCaT Keratinocytes against Staphylococcus aureus Induced Damage

“…The antibacterial activity of flavuside B was evaluated as described previously [37] according to the method adopted by the Clinical and Laboratory Standards Institute (CLSI) with a slight modification of the medium.…”

Synthesis, Cytotoxic Activity Evaluation and Quantitative Structure-ActivityAnalysis of Substituted 5,8-Dihydroxy-1,4-naphthoquinones and Their O- and S-Glycoside Derivatives Tested against Neuro-2a Cancer Cells

“…In our previous study, a series of new, tetracyclic oxathiine-fused quinone-thioglycoside conjugates based on biologically active 1,4-naphthoquinones (chloro-, hydroxy-, and methoxysubstituted) was synthesized and characterized. These compounds showed relatively high cytotoxic activity toward various types of cancer cells such as HeLa, Neuro-2a and mouse ascites Ehrlich carcinoma, and mouse normal epithelial cell line Jb6 Cl 41-5a without pronounced selectivity for a certain type of tumor cells [29]. The positive effect of heterocyclization with mercaptosugars on cytotoxic activity for a group of 1,4-naphthoquinones was observed.…”

“…To improve their solubility and achieve atargeted action, naphthoquinones can easily be converted into Oand S-glycosides [26] or nonglycoside Oand S-carbohydrate conjugates with promising cytotoxic activity and selectivity [27][28][29]. Well-developed methods of chemical transformation of NQs and their biological activities have led to a number of works describing quantitative structure-activity relationship (QSAR)analyses of the cytotoxicity of NQs with various structures.…”

Evaluation Of Differences Between Extracted And Synthesized Compounds On The Juglone Example

“…They are found not only in plants and lichens but also in animals. A vast variety of naphthoquinones that exhibit antitumor (Dyshlovoy, et al, 2019), antimicrobial (Sabutski et al, 2020), antiparasitic, antiinflammatory, antifungal, and trypanocidal activities (Dayronas & Zilfikarov, 2011) have been discovered to date. There are also several medicinal drugs with the main active agents being naphthoquinones, such as histochrome, vikasol, and atovaquone (also known under the trade name of Merpon) (Hughes et al, 1993).…”