Antimicrobial and Anti-Oxidative Activities of 12-Arylbenzoacridines

https://doi.org/10.22146/ijc.53411

Boonsong Wungsintaweekul(1*), Kayoko Abe(2), Rintaro Koga(3), Yoshinori Katakura(4), Kohei Torikai(5)

(1) School of Pharmacy, Walailak University, 222 Thaiburi, Thasala, Nakhon Si Thammarat 80161, Thailand
(2) Graduate School of Systems Life Sciences, Kyushu University, 744 Motooka, Nishi-ku, Fukuoka 819-0395, Japan
(3) Department of Chemistry, Graduate School and Faculty of Science, Kyushu University, 744 Motooka, Nishi-ku, Fukuoka 819-0395, Japan
(4) Faculty of Agriculture, Kyushu University, 744 Motooka, Nishi-ku, Fukuoka 819-0395, Japan
(5) Department of Chemistry, Graduate School and Faculty of Science, Kyushu University, 744 Motooka, Nishi-ku, Fukuoka 819-0395, Japan
(*) Corresponding Author

Abstract


Searching biologically active compounds has been one of the major duties of organic chemists. We previously constructed a library of synthetic 12-arylbenzoacridines and found estrogenic and anti-estrogenic agents. With taking the shot-gun approach into consideration, further exploration for bioactive species in the above library was carried out. As a result, new antibacterial agents against S. aureus (MIC = 16 μM), E. coli (MIC = 7.8 μM), E. faecalis (MIC = 0.98 μM), and A. baumannii (MIC = 31 μM) were found. Moreover, we also unveiled that some of the tested compounds exhibit cell-based anti-oxidative activity. These results clearly show a good potential of 12-arylbenzoacridines as novel pharmacophores, which is useful to establish various medicines.


Keywords


benzoacridine; antibacterial; shotgun approach; antioxidant



References

[1] Mohs, R.C., and Greig, N.H., 2017, Drug discovery and development: Role of basic biological research, Alzheimers Dement., 3 (4), 651-657.

[2] Gilberg, E., and Bajorath, J., 2019, Recent progress in structure-based evaluation of compound promiscuity, ACS Omega, 4 (2), 2758–2765.

[3] Proschak, E., Stark, H., and Merk, D., 2019, Polypharmacology by design: A medicinal chemist's perspective on multitargeting compounds, J. Med. Chem., 62 (2), 420–444.

[4] Bolognesi, M.L., and Cavalli, A., 2016, Multitarget drug discovery and polypharmacology, ChemMedChem, 11 (12), 1190–1192.

[5] Rosini, M., 2014, Polypharmacology: The rise of multitarget drugs over combination therapies, Future Med. Chem., 6 (5), 485–487.

[6] Anighoro, A., Bajorath, J., and Rastelli, G., 2014, Polypharmacology: Challenges and opportunities in drug discovery, J. Med. Chem., 57 (19), 7874–7887.

[7] Reddy, A.S., and Zhang, S., 2013, Polypharmacology: Drug discovery for the future, Expert Rev. Clin. Pharmacol., 6 (1), 41–47.

[8] Peters, J.U., 2013, Polypharmacology–foe or friend?, J. Med. Chem., 56 (22), 8955–8971.

[9] Hopkins, A.L., 2008, Network pharmacology: The next paradigm in drug discovery, Nat. Chem. Biol., 4 (11), 682–690.

[10] Torikai, K., Otsuka, Y., Nishimura, M., Sumida, M., Kawai, T., Sekiguchi, K., and Ueda, I., 2008, Synthesis and DNA cleaving activity of water-soluble non-conjugated thienyl tetraynes, Bioorg. Med. Chem., 16 (10), 5441–5451.

[11] Kimura, H., Torikai, K., and Ueda, I., 2009, Thermal cyclization of nonconjugated aryl–yne–carbodiimide furnishing a dibenzonaphthyridine derivative, Chem. Pharm. Bull., 57 (4), 393–396.

[12] Koga, R., Oishi, T., and Torikai, K., 2015, Tuned classical thermal aromatization furnishing an estrogenic benzoacridine, Synlett, 26 (20), 2801–2805.

[13] Torikai, K., Koga, R., Liu, X., Umehara, K., Kitano, T., Watanabe, K., Oishi, T., Noguchi, H., and Shimohigashi, Y., 2017, Design and synthesis of benzoacridines as estrogenic and anti-estrogenic agents, Bioorg. Med. Chem., 25 (20), 5216–5237.

[14] Motohashi, N., Sakagami, H., Kurihara, T., Ferenczy, L., Csuri, K., and Molnar, J., 1992, Antimicrobial activity of phenothiazines, benzo[a]phenothiazines and benz[c]acridines, Anticancer Res., 12 (4), 1207–1210.

[15] Molnar, J., Sakagami, H., and Motohashi, N., 1993, Diverse biological activities displayed by phenothiazines, benzo[a]phenothiazines and benz[c]acridines, Anticancer Res., 13 (4), 1019–1025.

[16] Molnar, J., Mandi, Y., Petri, I., Petofi, S., Sakagami, H., Kurihara, T., and Motohashi, N., 1993, Immunomodulation activity of phenothiazines, benzo[a]phenothiazines and benz[c]acridines, Anticancer Res., 13 (2), 439–442.

[17] Balouiri, M., Sadiki, M., and Ibnsouda, S.K., 2016, Methods for in vitro evaluating antimicrobial activity: A review, J. Pharm. Anal., 6 (2), 71–79.

[18] Braca, A., De Tommasi, N., Di Bari, L., Pizza, C., Politi, M., and Morelli, I., 2001, Antioxidant principles from Bauhinia tarapotensis, J. Nat. Prod., 64 (7), 892–895.

[19] Zhao, C., Sakaguchi, T., Fujita, K., Ito, H., Nishida, N., Nagatomo, A., Tanaka-Azuma, Y., and Katakura, Y., 2016, Pomegranate-derived polyphenols reduce reactive oxygen species production via SIRT3-mediated SOD2 activation, Oxid. Med. Cell. Longevity, 2016, 2927131.

[20] Tong, S.Y.C., Davis, J.S., Eichenberger, E., Holland, T.L., and Fowler, V.G.Jr., 2015, Staphylococcus aureus infections: Epidemiology, pathophysiology, clinical manifestations, and management, Clin. Microbiol. Rev., 28 (3), 603–661.

[21] Hennekinne, J.A., De Buyser, M.L., and Dragacci, S., 2012, Staphylococcus aureus and its food poisoning toxins: Characterization and outbreak investigation, FEMS Microbiol. Rev., 36 (4), 815–836.

[22] Croxen, M.A., Law, R.J., Scholz, R., Keeney, K.M., Wlodarska, M., and Finlay, B.B., 2013, Recent advances in understanding enteric pathogenic Escherichia coli, Clin. Microbiol. Rev., 26 (4), 822–880.

[23] Anderson, A.C., Jonas, D., Huber, I., Karygianni, L., Wölber, J., Hellwig, E., Arweiler, N., Vach, K., Wittmer, A., and Al-Ahmad, A., 2016, Enterococcus faecalis from food, clinical specimens, and oral sites: Prevalence of virulence factors in association with biofilm formation, Front. Microbiol., 6, 1534.

[24] Paczosa, M.K., and Mecsas, J., 2016, Klebsiella pneumoniae: Going on the offense with a strong defense, Microbiol. Mol. Biol. Rev., 80 (3), 629–661.

[25] Howard, A., O'Donoghue, M., Feeney, A., and Sleator, R.D., 2012, Acinetobacter baumannii; an emerging opportunistic pathogen, Virulence, 3 (3), 243–250.

[26] Duraisingham, S.S., Hanson, S., Buckland, M., Grigoriadou, S., and Longhurst, H.J., 2014, Pseudomonas infection in antibody deficient patients, Eur. J. Microbiol. Immunol., 4 (4), 198–203.

[27] Martins, N., Barros, L., Henriques, M., Silva, S., and Ferreira, I.C.F.R., 2015, In vivo anti-candida activity of phenolic extracts and compounds: Future perspectives focusing on effective clinical interventions, BioMed Res. I., 2015, 247382.

[28] Ajani, O.O., Joseph, O.E., Iyaye, K.T., October, N., Aderohunmu, D.V., Olorunshola, S.J., and Audu, O.Y., 2020, Facile synthesis, characterization and in vitro antibacterial efficacy of functionalized 2-substituted benzimidazole motifs, Indones. J. Chem., 20 (1), 72–87.



DOI: https://doi.org/10.22146/ijc.53411

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