Antioxidant and Antimicrobial Potential of 1,8-Naphthyridine Based Scaffolds: Design, Synthesis and in Silico Simulation Studies within Topoisomerase II
Corresponding Author
Assoc. Prof. Dr. Nadia A. A. Elkanzi
Chemistry Department, college of Science, Jouf University, 2014 Sakaka, Saudi Arabia
Search for more papers by this authorAssist. Prof. Dr. Hajer Hrichi
Chemistry Department, college of Science, Jouf University, 2014 Sakaka, Saudi Arabia
Search for more papers by this authorAssist. Prof. Dr. Alaa Muqbil Alsirhani
Chemistry Department, college of Science, Jouf University, 2014 Sakaka, Saudi Arabia
Search for more papers by this authorAssoc. Prof. Dr. Rania B. Bakr
Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Beni-Suef University, 62514 Beni-Suef, Egypt
Search for more papers by this authorCorresponding Author
Assoc. Prof. Dr. Nadia A. A. Elkanzi
Chemistry Department, college of Science, Jouf University, 2014 Sakaka, Saudi Arabia
Search for more papers by this authorAssist. Prof. Dr. Hajer Hrichi
Chemistry Department, college of Science, Jouf University, 2014 Sakaka, Saudi Arabia
Search for more papers by this authorAssist. Prof. Dr. Alaa Muqbil Alsirhani
Chemistry Department, college of Science, Jouf University, 2014 Sakaka, Saudi Arabia
Search for more papers by this authorAssoc. Prof. Dr. Rania B. Bakr
Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Beni-Suef University, 62514 Beni-Suef, Egypt
Search for more papers by this authorAbstract
A series of spiro β-Lactams (4 a–c, 7 a–c) and thiazolidinones (5 a–c, 8 a–c) possessing 1,8-naphthyridine moiety were synthesized in this study. The structure of the newly synthesized compounds has been confirmed by IR, 1H-NMR, 13C NMR, mass spectra, and elemental analysis. The synthesized compounds were tested in vitro for their antibacterial and antifungal activity against various strains. The antimicrobial data showed that most of the compounds displayed good efficacy against both bacteria and fungi. The structure-activity relationship (SAR) studies suggested that the presence of electron-withdrawing chloro (3 b, 4 b, and 5 b) and nitro groups (7 b, 8 b) at the para position of the phenyl ring improved the antimicrobial activity of the compounds. The free radical scavenging assay showed that all the synthesized compounds exhibited significant antioxidant activity on DPPH. Compounds 8 b (IC50=17.68±0.76 μg/mL) and 4 c (IC50=18.53±0.52 μg/mL) showed the highest antioxidant activity compared to ascorbic acid (IC50=15.16±0.43 μg/mL). Molecular docking studies were also conducted to support the antimicrobial and SAR results.
Graphical Abstract
Conflict of interests
The authors declare no conflict of interest.
Open Research
Data Availability Statement
The data that support the findings of this study are available from the corresponding author upon reasonable request.
References
- 1P. Rani, D. K. Pal, R. R. Hegde, S. R. Hashim, Hem. Ind. 2015, 69, 405–415.
- 2M. A. Abdelgawad, A. Musa, A. H. Almalki, S. I. Alzarea, E. M. Mostafa, M. M. Hegazy, et al., Drug Des. Dev. Ther. 2021, 15, 2325.
- 3R. A. Shinde, V. A. Adole, R. D. Amrutkar, S. R. Tambe, B. S. Jagdale, Polycyclic Aromat. Compd. 2023, 1–23.
- 4R. A. Shinde, V. A. Adole, B. S. Jagdale, J. Mol. Struct. 2024, 1300, 137096.
- 5R. H. Waghchaure, V. A. Adole, J. Mol. Struct. 2024, 1296, 136724.
- 6K. B. Gangurde, R. A. More, V. A. Adole, D. S. Ghotekar, J. Mol. Struct. 2024, 1299, 136760.
- 7S. S. Choudhury, S. Jena, D. K. Sahoo, S. Shekh, R. K. Kar, A. Dhakad, et al., ACS Omega 2021, 6, 19304–19313.
- 8M. A. Alanazi, W. A. Arafa, I. O. Althobaiti, H. A. Altaleb, R. B. Bakr, N. A. Elkanzi, ACS Omega 2022, 7, 27674–27689.
- 9N. A. Elkanzi, I. H. El Azab, R. B. Bakr, Polycyclic Aromat. Compd. 2022, 42(9), 6760–6779.
- 10M. T. Riaz, M. Yaqub, S. Javed, D. Hussain, M. N. Ashiq, Z. Shafiq, J. Taibah Univ. Sci. 2021, 15, 559–566.
- 11K. Vennila, B. Selvakumar, V. Satish, D. Sunny, S. Madhuri, K. Elango, Med. Chem. Res. 2021, 30, 133–141.
- 12N. Kaur, Synth. Commun. 2015, 45, 35–69.
- 13M. Andrews, R. H. Laye, S. J. Pope, Transition Met. Chem. 2009, 34, 493–497.
- 14S. Abu-Melha, Acta Chim. Slov. 2017, 64, 919–930.
- 15A. A. Mohammed, G. A. Suaifan, M. B. Shehadeh, P. N. Okechukwu, Drug Dev. Res. 2019, 80, 179–186.
- 16T. R. Makhanya, R. M. Gengan, A. Ata, Synth. Commun. 2019, 49, 823–835.
- 17B. Sakram, B. Sonyanaik, K. Ashok, S. Rambabu, D. Ravi, A. Kurumanna, et al., Res. Chem. Intermed. 2017, 43, 1881–1892.
- 18N. A. A. Elkanzi, A. A. Ghoneim, R. B. Bakr, PharmaChem 2019, 11, 6–13.
- 19V. K. Gurjar, D. Pal, RSC Adv. 2020, 10, 13907–13921.
- 20V. Kumar, M. Jaggi, A. T. Singh, A. Madaan, V. Sanna, P. Singh, et al., Eur. J. Med. Chem. 2009, 44, 3356–3362.
- 21A. Madaan, V. Kumar, R. Verma, A. T. Singh, S. Jain, M. Jaggi, Int. Immunopharmacol. 2013, 15, 606–613.
- 22A. N. Al-romaizan, T. S. Jaber, N. S. Ahmed, Open Chemistry 2019, 17, 943–954.
- 23L. Fu, X. Feng, J.-J. Wang, Z. Xun, J.-D. Hu, J.-J. Zhang, et al., ACS Comb. Sci. 2015, 17, 24–31.
- 24A. K. Elansary, A. A. Moneer, H. H. Kadry, E. M. Gedawy, J. Chem. Res. 2014, 38, 147–153.
- 25E. P. Garvey, B. A. Johns, M. J. Gartland, S. A. Foster, W. H. Miller, R. G. Ferris, et al., Antimicrob. Agents Chemother. 2008, 52, 901–908.
- 26I. P. Singh, S. Kumar, S. Gupta, Med. Chem. 2017, 13, 430–438.
- 27J. A. Al jamal, M. Badawneh, Arch. Pharm. 2003, 336, 285–292.
- 28B. K. Gautam, A. Jindal, A. K. Dhar, R. Mahesh, Pharmacol. Biochem. Behav. 2013, 109, 91–97.
- 29R. Mahesh, A. K. Dhar, A. Jindal, S. Bhatt, Can. J. Physiol. Pharmacol. 2013, 91, 848–854.
- 30J. D. Gohil, H. B. Patel, M. P. Patel, RSC Adv. 2016, 6, 74726–74733.
- 31B. Sakram, K. Ashok, S. Rambabu, B. Sonyanaik, D. Ravi, Russ. J. Gen. Chem. 2017, 87, 1794–1799.
- 32A. B. Petersen, M. H. Rønnest, T. O. Larsen, M. H. Clausen, Chem. Rev. 2014, 114, 12088–12107.
- 33F. Golmohammadi, S. Balalaie, V. Fathi Vavsari, M. U. Anwar, A. Al-Harrasi, J. Org. Chem. 2020, 85, 13141–13152.
- 34Y.-J. Zheng, C. M. Tice, Expert Opin. Drug Discovery 2016, 11, 831–834.
- 35R. Rios, Chem. Soc. Rev. 2012, 41, 1060–1074.
- 36A. Ding, M. Meazza, H. Guo, J. W. Yang, R. Rios, Chem. Soc. Rev. 2018, 47, 5946–5996.
- 37H. Abdellaoui, J. Xu, Tetrahedron 2014, 70, 4323–4330.
- 38J. W. Skiles, D. McNeil, Tetrahedron Lett. 1990, 31, 7277–7280.
- 39A. Verma, S. K. Saraf, Eur. J. Med. Chem. 2008, 43, 897–905.
- 40M. Djukic, M. Fesatidou, I. Xenikakis, A. Geronikaki, V. T. Angelova, V. Savic, et al., Chem.-Biol. Interact. 2018, 286, 119–131.
- 41R. B. Bakr, N. A. Elkanzi, J. Heterocycl. Chem. 2020, 57, 2977–2989.
- 42H. Zhang, J. Zhang, W. Qu, S. Xie, L. Huang, D. Chen, et al., Front. Chem. 2020, 8, 598.
- 43A. Türe, M. Ergül, M. Ergül, A. Altun, İ. Küçükgüzel, Mol. Diversity 2021, 25, 1025–1050.
- 44S. B. Bari, S. D. Firake, Anti-Inflammatory Anti-Allergy Agents Med. Chem. 2016, 15, 44–53.
- 45N. Saini, A. Sharma, V. K. Thakur, C. Makatsoris, A. Dandia, M. Bhagat, et al., Curr. Res. Green Sustain. Chem. 2020, 3, 100021.
10.1016/j.crgsc.2020.100021 Google Scholar
- 46K. D. Asgaonkar, S. M. Patil, T. S. Chitre, V. N. Ghegade, S. R. Jadhav, S. S. Sande, et al., Curr. Comput.-Aided Drug Des. 2019, 15, 252–258.
- 47V. Ravichandran, A. Jain, K. S. Kumar, H. Rajak, R. K. Agrawal, Chem. Biol. Drug Des. 2011, 78, 464–470.
- 48N. A. A. Elkanzi, H. A. A. E.-M. Yosef, N. M. M. Mohamed, Eur. J. Chem. 2013, 4, 195–202.
10.5155/eurjchem.4.3.195-202.777 Google Scholar
- 49R. B. Bakr, N. A. Elkanzi, Lett. Drug Des. Discovery 2022, 19, 675–690.
- 50N. A. Elkanzi, H. Hrichi, R. B. Bakr, O. Hendawy, M. M. Alruwaili, E. D. Alruwaili, et al., J. Iran. Chem. Soc. 2021, 18, 977–991.
- 51N. A. Elkanzi, R. B. Bakr, Lett. Drug Des. Discovery 2020, 17, 1538–1551.
10.2174/1570180817999200802033351 Google Scholar
- 52H. Hrichi, E. N. A. Ahmed, B. R. Badawy, Chem. J. Mold. 2020, 15, 86–94.
- 53N. A. Elkanzi, H. Hrichi, R. A. Alolayan, W. Derafa, F. M. Zahou, R. B. Bakr, ACS Omega 2022, 7, 27769–27786.
- 54M. A. Abdelgawad, M. M. Al-Sanea, A. Musa, M. Elmowafy, A. K. El-Damasy, A. A. Azouz, et al., J. Inflamm. Res. 2022, 15, 451.
- 55M. A. Abdelgawad, A. Musa, A. H. Almalki, S. I. Alzarea, E. M. Mostafa, M. M. Hegazy, et al., Drug Des. Dev. Ther. 2021, 15, 2325–2337.
- 56R. B. Bakr, A. Mehany, Molbank 2016, 2016, M915.
- 57B. B. Rania, A. Nadia, A. G. Amira, M. Shaima, Heterocycles 2018, 96, 1941–1957.
- 58N. A. A. Elkanzi, A. A. Ghoneim, R. B. Bakr, PharmaChem 2019, 11, 6–13.
- 59B. Mathew, D. G. Parambi, M. Singh, O. M. Hendawy, M. M. Al-Sanea, R. B. Bakr, Protopine. Naturally Occurring Chemicals Against Alzheimer's Disease: Elsevier; 2021. p. 167–174.
10.1016/B978-0-12-819212-2.00014-1 Google Scholar
- 60M. E. Shaker, H. A. Goma, I. Alsalahat, N. A. Elkanzi, A. A. Azouz, M. S. Abdel-Bakky, et al., J. Biomol. Struct. Dyn. 2023, 1–14.
- 61N. A. Elkanzi, A. Farag, N. Roushdy, A. Mansour, Optik 2020, 216, 164882.
- 62N. F. Santos-Sánchez, R. Salas-Coronado, C. Villanueva-Cañongo, B. Hernández-Carlos, Antioxidants 2019, 10, 1–29.
- 63I. R. Ilyasov, V. L. Beloborodov, I. A. Selivanova, R. P. Terekhov, Int. J. Mol. Sci. 2020, 21, 1131.
- 64S. Santosh Kumar, K. Priyadarsini, K. Sainis, Redox Rep. 2002, 7, 35–40.
- 65K. N. Mohana, C. B. P. Kumar, Int. Sch. Res. Notices 2013, 2013.
- 66E. Bendary, R. Francis, H. Ali, M. Sarwat, S. El Hady, Ann. Agric. Sci. 2013, 58, 173–181.
10.1016/j.aoas.2013.07.002 Google Scholar
- 67S. A. Komykhov, K. S. Ostras, A. R. Kostanyan, S. M. Desenko, V. D. Orlov, H. Meier, J. Heterocycl. Chem. 2005, 42, 1111–1116.
- 68V. Panteleon, I. K. Kostakis, P. Marakos, N. Pouli, I. Andreadou, Bioorg. Med. Chem. Lett. 2008, 18, 5781–5784.
- 69A. Aouf, S. Bouaouina, M. A. Abdelgawad, M. A. Abourehab, A. Farouk, Antibiotics 2022, 11, 1317.
