Abstract
The 1,3-benzodioxol moiety present in safrole, apiole, and myristicin essential oils and benzodioxol derivatives have shown a wide range of biological activities including antiepileptic, analgesic, antituberculosis, and antimicrobial potentials. Here, we have tested the antibacterial and antioxidant activities of a series of benzodioxol derivatives. Twelve compounds of aryl acetate and acetic acid benzodioxol were evaluated against different types of bacterial strains, including Staphylococcus aureus, Escherichia coli, Enterococcus faecalis, and Pseudomonas aeruginosa using the broth dilution method, and the most potent compound was 3e, which exhibited the bacterial growth of with MICs of 125 (S. aureus), 250 (E. coli), 220 (E. faecalis), and 100 µg/mL (P. aeruginosa). Our positive control, cinoxacin, had MICs of 250 (S. aureus), 250 (E. coli), 250 (E. faecalis), and 500 µg/mL (P. aeruginosa). Antioxidant activity was evaluated for the synthesized compounds utilizing the DPPH assay. The 3a compound was the most active with an IC50 value of 21.44 µg/mL, while the IC50 values of compounds 3b, 3e, and 3f were 96.07, 58.45, and 72.17 µg/mL, respectively. In contrast, all compounds with the acetic acid functional group had weaker activity, with an IC50 range of 193.52–289.78 µg/mL compared with the potent antioxidant agent Trolox (IC50 = 1.93 µg/mL). In the present paper, new benzodioxol-based aryl acetate and acetic acid derivatives were evaluated for their antibacterial and antioxidant activities. The outcomes revealed that the antibacterial and antioxidant properties of some of the synthesized benzodioxol aryl acetate and acetic acid derivatives can be considered as valuable materials for the pharmaceutical industry. Thus, these molecules should be further evaluated in vivo as lead compounds for the discovery of new drug candidates.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
Data Availability
All the utilized data to support the findings of the current study are included in the article.
References
Li, B.: Bacteria antibiotic resistance: new challenges and opportunities for implant-associated orthopedic infections. J. Orthop. Res. 36, 22–32 (2018). https://doi.org/10.1002/jor.23656
Manyi-Loh, C.; Mamphweli, S.; Meyer, E.; Okoh, A.J.M.: Antibiotic use in agriculture and its consequential resistance in environmental sources: potential public health implications. Molecules 23, 795 (2018). https://doi.org/10.3390/molecules23040795
van Wietmarschen, H.: Integrative approaches to antimicrobial resistance. Eur. J. Integr. Med. 39, 101191 (2020)
Tas, S.; Tas, B.; Bassalat, N.; Jaradat, N.: In-vivo, hypoglycemic, hypolipidemic and oxidative stress inhibitory activities of Myrtus communis L. fruits hydroalcoholic extract in normoglycemic and streptozotocin-induced diabetic rats. Biomed. Res. 29, 2727–2734 (2018)
Detsi, A., et al.: Design and synthesis of novel quinolinone-3-aminoamides and their r-lipoic acid adducts as antioxidant and anti-inflammatory agents. J. Med. Chem. 50, 2450–2458 (2007). https://doi.org/10.1021/jm061173n
Sies, H.: Strategies of antioxidant defense. Eur J Biochem 215, 213–219 (1993)
Solano, F.; Briganti, S.; Picardo, M.; Ghanem, G.: Hypopigmenting agents: an updated review on biological, chemical and clinical aspects. Pigment Cell Res. 19, 550–571 (2006). https://doi.org/10.1111/j.1600-0749.2006.00334.x
Weiss, J.F.; Landauer, M.R.: Radioprotection by antioxidantsa. Ann. N. Y. Acad. Sci. 899, 44–60 (2006). https://doi.org/10.1111/j.1749-6632.2000.tb06175.x
Kumar, A.; Maurya, R.A.; Sharma, S.; Kumar, M.; Bhatia, G.: Synthesis and biological evaluation of N-aryl-1,4-dihydropyridines as novel antidyslipidemic and antioxidant agents. Eur. J. Med. Chem. 45, 501–509 (2010). https://doi.org/10.1016/j.ejmech.2009.10.036
Abu-Hashem, A.A.; El-Shehry, M.F.; Badria, F.A.: Design and synthesis of novel thiophenecarbohydrazide, thienopyrazole and thienopyrimidine derivatives as antioxidant and antitumor agent. Acta Pharm. 60, 311–323 (2010)
Berg, R.V.D.; Haenen, G.; Berg, H.V.D.; Bast, A.: Applicability of an improved Trolox equivalent antioxidant capacity (TEAC) assay for evaluation of antioxidant capacity measurements of mixtures. Food Chem. 66, 511–517 (1999)
Hong, W.-S., et al.: The antioxidant effect of rebamipide on oxygen free radical production by H. pylori-activated human neutrophils: in comparison with N-acetylcysteine, ascorbic acid and glutathione. Pharmacol. Res. 44, 293–297 (2001)
da Silva, L.M.M.G., et al.: New 1, 3-benzodioxole derivatives: synthesis, evaluation of in vitro schistosomicidal activity and ultrastructural analysis. Chem. Biol. Interact. 283, 20–29 (2018)
Deshpande, S.R.; Nagrale, S.N.; Patil, M.V.; Chavan, S.S.: Novel 3,4-methylenedioxybenzene scaffold incorporated 1,3,5-trisubstituted-2-pyrazolines: Synthesis, characterization and evaluation for chemotherapeutic activity. Indian J. Pharm. Sci. 77, 24 (2015). https://doi.org/10.4103/0250-474x.151588
Espahbodinia, M., et al.: Development of novel N-3-bromoisoxazolin-5-yl substituted 2,3-benzodiazepines as noncompetitive AMPAR antagonists. Bioorg. Med. Chem. 25, 3631–3637 (2017). https://doi.org/10.1016/j.bmc.2017.05.036
Khayyat, S.A.: Photosynthesis of dimeric cinnamaldehyde, eugenol, and safrole as antimicrobial agents. J. Saudi Chem. Soc. 17, 61–65 (2013). https://doi.org/10.1016/j.jscs.2011.07.014
Lima, P.C.; Lima, L.M.; Silva, K.C.M.; Léda, P.H.O.; Miranda, A.L.P.; Fraga, C.A.M.; Barreiro, E.J.: Synthesis and analgesic activity of novel N-acylarylhydrazones and isosters, derived from natural safrole. Eur. J. Med. Chem. 35, 187–203 (2000)
Miller, E.C.; Swanson, A.B.; Phillips, D.H.; Fletcher, T.L.; Liem, A.; Miller, J.A.: Structure-activity studies of the carcinogenicities in the mouse and rat of some naturally occurring and synthetic alkenylbenzene derivatives related to Safrole and Estragol. Can. Res. 43, 1124–1134 (1983)
Rollas, S.; Küçükgüzel, S.G.: Biological activities of hydrazone derivatives. Molecules 12, 1910–1939 (2007)
Leite, A.C.L.; da Silva, K.P.; Brondani, D.J.: Synthesis of 1,3-benzodioxole derivatives containing a amino acid moiety in side chain. Heterocycl. Commun. 7(555–558), 5 (2001)
Wayne, P.: Performance standards for antimicrobial susceptibility testing of bacteria isolated from aquatic animals vol second informational supplementstandards. Clinical and Laboratory Standards Institute, USA (2014)
Bouyahya, A.; El Moussaoui, N.; Abrini, J.; Bakri, Y.; Dakka, N.: Determination of phenolic contents, antioxidant and antibacterial activities of strawberry tree (Arbutus unedo L.) leaf extracts. Br. Biotechnol. J. 14, 1–10 (2016)
Hawash, M.; Jaradat, N.; Hameedi, S.; Mousa, A.: Design, synthesis and biological evaluation of novel benzodioxole derivatives as COX inhibitors and cytotoxic agents. BMC Chem. 14, 1–9 (2020)
Jaradat, N.; Qneibi, M.; Hawash, M.; Sawalha, A.; Qtaishat, S.; Hussein, F.; Issa, L.: Chemical composition, antioxidant, antiobesity, and antidiabetic effects of Helichrysum sanguineum (L.) Kostel. from Palestine. Arab. J. Sci. Eng. 46, 1–11 (2020)
Cheng, G.; Hao, H.; Xie, S.; Wang, X.; Dai, M.; Huang, L.; Yuan, Z.: Antibiotic alternatives: the substitution of antibiotics in animal husbandry? Front. Microb. 5, 217 (2014)
El-Behairya, M.; Mazeedb, T.E.; El-Azzounya, A.A.; Aboul-Eneina, M.N.: Design, synthesis and antibacterial potential of 5-(benzo[d][1,3]dioxol-5-yl)-3-tert-butyl-1-substituted-4,5-dihydropyrazoles. Saudi Pharm. J. 23, 202–209 (2015). https://doi.org/10.1016/j.jsps.2014.1007.1009
Siddiqa, A.; Rehman, A.-u; Abbasi, M.A.; Rasool, S.; Khan, K.M.; Ahmad, I.; Afzal, S.: Synthesis and antibacterial evaluation of 2-(1, 3-Benzodioxol-5-ylcarbonyl) arylsulfonohydrazide derivatives. Tropical J. Pharm. Res. 13, 1689–1696 (2014)
Patrick, G.L.: An introduction to medicinal chemistry. Oxford University Press, Oxford (2013)
Assali, M.; Abualhasan, M.; Sawaftah, H.; Hawash, M.; Mousa, A.: Synthesis, biological activity, and molecular modeling studies of pyrazole and triazole derivatives as selective COX-2 inhibitors. J. Chem. (2020)
Qneibi, M.; Jaradat, N.; Hawash, M.; Olgac, A.; Emwas, N.: Ortho versus meta chlorophenyl-2, 3-benzodiazepine analogues: synthesis, molecular modeling, and biological activity as AMPAR antagonists. ACS Omega 5, 3588–3595 (2020)
Acknowledgments
The authors would like to thank King Fahad University of Petroleum and Minerals Kingdom of Saudi Arabia and An-Najah National University- Palestine for their support to accomplish this work.
Funding
None.
Author information
Authors and Affiliations
Contributions
All research was done by the authors.
Corresponding authors
Ethics declarations
Conflict of interest
The authors declare that there are no conflicts of interest.
Rights and permissions
About this article
Cite this article
Khalil, A., Jaradat, N., Hawash, M. et al. In Vitro Biological Evaluation of Benzodioxol Derivatives as Antimicrobial and Antioxidant Agents. Arab J Sci Eng 46, 5447–5453 (2021). https://doi.org/10.1007/s13369-021-05332-0
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s13369-021-05332-0