Docking Study for New 7-Aminocephalosporinic Acid Derivatives as Potential Inhibitors for β-Lactamases
Abstract
Background: Antibiotics with -Lactam rings (-Lactams), since they were discovered, have enhanced the typical treatment for bacterial infections. Though their resistance can quickly spread on a universal scale, bacterial resistance is primarily caused by the production of -lactamases. Hence, there is a serious demand to design and create new anti--lactamases or inhibitors. Nowadays, the use of -lactamase inhibitors with -lactams reduces this resistance. Aim and Methods: This work aimed to help in silico design and dock two new series of 7-aminocephalosporinic acid derivatives (Schiffs bases and amides) against both the TEM-1 and the IMP-1 -lactamases. Results: The results revolve around the possible enhanced activity of eight amides and six Schiff base compounds compared with the standard inhibitors (clavulanic acid, sulbactam, and avabactam). These compounds show promising docking interactions with an active pocket site in both enzymes. Conclosin: We can conclude that both the halogenated and the hydrophobic substituents, alone or when containing oxygen atoms, will potentiate the affinity and the binding ability of any compounds when they are added to their structures to act as -lactamase inhibitors.
References
- Abdul Hameed A, al-Rashida M, Uroos M, Ali SA and Khan KM. Schiff bases in medicinal chemistry: a patent review (2010-2015), Expert Opin Ther Pat, 2017, 27(1):63-79.
- Adesoji AT, Onuh JP and Okunye OL. Bacteria resistance to cephalosporins and its implication to public health. Journal of Bacteriology and Mycology, 2016;3(1):1021.
- Bonomo RA. b-Lactamases: A focus on current challenges. Cold Spring Harb. Perspect. Med., 2017; 7(1):a025239.
- Bousfield TW, Pearce KPR and Nyamini SB. Synthesis of amides from acid chlorides and amines in the bio-based solvent Cyrene. The Royal Society of Chemistry; Green Chem., 2019; 21:3675-3681
- Bush K. Past and present perspectives on betalactamases. Antimicrob. Agents Chemother. 2018; 62(10):18.
- Drawz SM and Bonomo RA. Three decades of b-lactamase inhibitors. american society for microbiology, Clinical Microbiology Reviews, 2010;23(7):160-201.
- Dunetz JR, Magano J and Weisenburger GA. Large-scale applications of amide coupling reagents for the synthesis of pharmaceuticals. Org. Process Res. Dev., 2016;20:140-177.
- Elshamy AA and Aboshanab KM. A review on bacterial resistance to carbapenems: epidemiology, detection and treatment options. Future Sci. OA, 2020;6(3),FSO438.
- Ferri M, Ranucci E, Romagnoli P and Giaccone V. Antimicrobial resistance: A global emerging threat to public health systems. Crit. Rev. Food Sci. Nutr., 2017;57:28572876.
- Gawehn E, Hiss JA and Schneider G. Deep learning in drug discovery. Mol. Inform., 2016,35:1-12.
- Gawehn E, Hiss JA and Schneider G. Deep learning in drug discovery. Mol. Inform., 2016;35:3-14.
- Halat DH and Moubareck CA. The current burden of carbapenemases: review of significant properties and dissemination among gram-negative bacteria. Antibiotics, 2020;9:186.
- Jubeh B, Breijyeh Z and Karaman R. Antibacterial Prodrugs to Overcome Bacterial Resistance. Molecules, 2020;25:1543.
- King AM. Discovery and characterization of novel beta-lactamase inhibitors. Ph.D. Thesis, McMaster University, Chemistry and Chemical Biology, 2016.
- Lin X, Li X and Lin X. A review on applications of computational methods in drug screening and design. Molecules, 2020;25:1375.
- Mahmood AAJ, Al-Iraqi MA and Abachi FT. Design, synthesis, and evaluation the anti--lactamase activity of new sulphathiazole-derived monobactam compounds. Iraqi Journal of Pharmacy,2020,17(1):19-36
- Mahmood AAJ, Al-Iraqi MA and Abachi FT. Fluorine important element in new drugs synthesis: Review Study.Iraqi Journal of Pharmacy, 2018;15(1):37-45.
- Mahmood AAJ, Al-Iraqi MA and Abachi FT. New 4,4-methylenedianiline monobactame compounds: Synthesis, antioxidant and antimicrobial activities evaluation, AIP Conference Proceedings, 2022;2660: 020024.
- Mahmood AAJ, Al-Iraqi MA and Al-Abacchi FT. Design, synthesis and anti--lactamase activity for new monobactam compounds. Materials Today: Proceedings,2021;42:1860-1866.
- Mahmood AAJ. Green synthesis of Schiff bases: a review study.Iraqi Journal of Pharmacy, 2022,18(2):180-193.
- Monaco M, Giani T, Raffone M, Arena F, Garcia FA, Pollini S, Grundmann H, Pantosti A, Rossolini GM. Colistin resistance superimposed to endemic carbapenem-resistant Klebsiella pneumoniae: a rapidly evolving problem in Italy, November 2013 to April 2014. Euro surveillance, 2014;19(42):20939.
- Olugbenga OO. Bacterial Resistance; A Perspective on Beta-Lactamase Enzymes. EC Microbiology, 2020;16(3):1-12.
- Reddy N, Shungube M, Arvidsson PI, Baijnath S, Kruger HG, et al. A 2018-2019 patent review of metallo beta-lactamase inhibitors, Expert Opinion on Therapeutic Patents, 2020;30(7). https://doi.org/10.1080/13543776.2020.1767070.
- Rossolini GM, Arena F, Pecile P, Pollini S. Update on the antibiotic resistance crisis. Curr. Opin. Pharmacol, 2014;18:56-60.
- Shah B, Modi P & Sagar SR. In Silico Studies On Therapeutic Agents For Covid-19: Drug Repurposing Approach. Life Sciences, 2020;252:117652.
- Singh GS and Sudheesh S. -Lactams in natural lactones and lactams: synthesis, occurrence and biological activity; Janecki, T., Ed.; Wiley-VCH, 2014:101145.