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. 2022 Nov 27;12(12):1765.
doi: 10.3390/biom12121765.

Anticancer, Antimicrobial, and Antioxidant Activities of Organodiselenide-Tethered Methyl Anthranilates

Batool Al-Abdallah  1 , Yasair S Al-Faiyz  1 , Saad Shaaban  1   2
Affiliations

Anticancer, Antimicrobial, and Antioxidant Activities of Organodiselenide-Tethered Methyl Anthranilates

Batool Al-Abdallah et al. Biomolecules. .

Abstract

Novel methyl anthranilate-based organodiselenide hybrids were synthesized, and their chemical structures were confirmed by state-of-the-art spectroscopic techniques. Their antimicrobial properties were assessed against Staphylococcus aureus, Escherichia coli, and Candida albicans microbial strains. Moreover, the antitumor potential was estimated against liver and breast carcinomas, as well as primary fibroblast cell lines. The Staphylococcus aureus and Candida albicans strains were more sensitive than Escherichia coli toward the OSe compounds. Interestingly, methyl 2-amino-5-(methylselanyl) benzoate (14) showed similar antifungal activity to the standard drug clotrimazole (IA% = 100%) and manifested promising antibacterial activity against E. coli (IA% = 91.3%) and S. aureus (IA% = 90.5%). Furthermore, the minimum inhibitory concentration experiments confirmed the antimicrobial activity of the OSe 14, which in turn was comparable to clotrimazole and ampicillin drugs. Interestingly, the anticancer properties were more pronounced in the HepG2 cells. The OSe 14 was the most cytotoxic (IC50 = 3.57 ± 0.1 µM), even more than the Adriamycin drug (IC50 = 4.50 ± 0.2 µM), and with therapeutic index (TI) 17 proposing its potential selectivity and safety. Additionally, OSe compounds 14 and dimethyl 5,5'-diselanediylbis(2-aminobenzoate) (5) exhibited promising antioxidants in the 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid (ABTS) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) in vitro assays with 96%, 92%, 91%, and 86% radical scavenging activities compared to 95% by vitamin C in the DPPH and ABTS assays, respectively. These results point to promising antimicrobial, anticancer, and antioxidant activities of OSe 14 and 5 and warrant further studies.

Keywords: anthranilic acid; anticancer; antimicrobial; antioxidant; organodiselenide; organoselenium.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
The structure of biologically relevant organoselenium and anthranilic acid analogs.
Scheme 1
Scheme 1
Preparation of compounds 2, 4, and 5. Reagents and conditions: (a) anthranilic acid (1) (29.1 mmol), MeOH (60 mL), conc.H2SO4 (4 mL), reflux for 48 h; (b) SeO2 (30 mmol), malononitrile (15 mmol), DMSO (10 mL), methyl 2-aminobenzoate (12.5 mmol) (2); (c) 2-amino-5-selenocyanatobenzoic acid (3) (29.1 mmol), MeOH (60 mL), conc.H2SO4 (4 mL), reflux for 48 h; (d) methyl 2-amino-5-selenocyanatobenzoate (4) (4 mmol), NaOH (4 mmol), EtOH, room temperature (15 mL).
Scheme 2
Scheme 2
Synthesis of diselenides 6, 7, 8, 9, and 10. Reagents and conditions: (a) compound 5 (2 mmol), HCl (3 mL), sodium nitrite (4.4 mmol), sodium acetate (2 g), H2O: EtOH (1:1), ethyl cyanoacetate (4.4 mmol); (b) THF (10 mL), acetic formic anhydride (36.3 mmol); (c) acetic anhydride (8 mL); (d) chloroacetyl chloride (4.4 mmol), K2CO3 (2 g), dry acetone (20 mL); (e) phenoxy acetyl chloride (2.2 mmol), dry ether (15 mL).
Scheme 3
Scheme 3
Synthesis of diselenides 11, 12, 13, 14, 15, and 16. Reagents and conditions: (a) Diselenide 5 (2 mmol), dry toluene (15 mL), maleic or succinic anhydride (4.4 mmol), room temperature; (b) respective amide-acids (0.5 mmol), acetic anhydride (5 mL), sodium acetate (250 mg); 50–60 °C; (c) diselenide 5 (2 mmol), halo derivatives (4.4 mmol), NaBH4 (6 mmol), EtOH (25 mL), room temperature.
Figure 2
Figure 2
The OSe compounds redox activities assessment using the ABTS and DPPH experiments. All tests are mean ± SD. ABTS experiment: absorbance was followed at 734 nm for OSe compounds (50 µL, 1 mM in MeOH) and ABTS solution (60 µL). DPPH experiment: Absorbance was monitored after 30 min at 517 nm for OSe compounds (200 µL, 1 mM in MeOH) and DPPH (400 µL).
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