In Silico Molecular Docking, Synthesis and Preliminary Evaluation of Antibacterial Activity of Levofloxacin Carboxamides with Certain Amino Acids


  • Sarah Abdul-Razzaq makki Department of pharmaceutical chemistry, College of Pharmacy / Al- Mustansiriyah University
  • Shakir M Alwan Department of Pharmacy, Al-Farabi University College
  • Mayada H. Al-Qaissy Department of pharmaceutical chemistry, College of Pharmacy / Al- Mustansiriyah University



Levofloxacin, Glycine, Serine, Histidine, DNA gyrase, Molecular Docking, ADME Studies


Levofloxacin carboxamides with certain amino acids were prepared through an amide linkage to the amino acid (glycine, histidine, or serine). These carboxamides were subjected to an in silico molecular docking evaluation on


DNA gyrase to predict their antibacterial activity using the GOLD suite. The binding affinities were very significant and encouraged the synthesis of the suggested carboxamides for intensive evaluation. These carboxamides were also subjected to Swiss ADME software to predict their ADME parameters. Levofloxacin carboxamides were prepared in high yield, and their chemical structures were confirmed by spectral analysis, such as 1H-NMR, 13C-NMR and FT-IR spectroscopy. Antibacterial activities were evaluated for the new carboxamides against two G-ve (Klebsiella and P. aeruginosa) and one G+ve (Streptococcus pneumonia) bacteria. When compared to levofloxacin, all of the synthesized carboxamides 1-3 demonstrated good activity against three types of bacteria. These carboxamides showed significant antibacterial activities against S. pneumoniae and lower activities against Klebsiella.


- Brar R.K, Jyoti U, Patil R.K, Patil H.C. Fluoroquinolone antibiotics: An overview. Andersson MI, MacGowan AP J. 2020;2(1):26–30.

- Ezelarab H.A.A, Abbas S.H, Hassan H.A, Abuo-Rahma GEDA. Recent updates of fluoroquinolones as antibacterial agents. Arch Pharm (Weinheim). 2018;351(9):1–13.

- Shenoy E.S, Macy E, Rowe T, Blumenthal K.G. Evaluation and Management of Penicillin Allergy: A Review. JAMA - J Am Med Assoc. 2019;321(2):188–199.

- Rusu A, Lungu I.A, Moldovan O.L, Tanase C, Hancu G. Structural characterization of the millennial antibacterial (Fluoro)quinolones—shaping the fifth generation. Pharmaceutics. 2021;13(8):1–37.

- Fedorowicz J, Sączewski J. Modifications of quinolones and fluoroquinolones: hybrid compounds and dual-action molecules. Monatshefte fur

Chemie. 2018;149(7): 1199–1245.

- Hiasa H. DNA topoisomerases as targets for antibacterial agents. Methods Mol Biol. 2018;1703:47–62.

- Zahoor A.F, Yousaf M, Siddique R, Ahmad S, Naqvi SAR, Rizvi SMA. Synthetic strategies toward the synthesis of enoxacin-, levofloxacin-, and gatifloxacin-based compounds: A review. Synth Commun. 2017;47(11):1021–1039.

- Li J, Zheng T.C, Jin Y, Xu J.G, Yu J.G, Lv Y.W. Synthesis, molecular docking and biological evaluation of quinolone derivatives as novel anticancer agents. Chem Pharm Bull. 2018;66(1):55–60.

- Sun J ping, Shi Z yu, Liu S meng, Kang Y hua, Hu G qiang, Huangfu C shen, et al. Trimethoxy-benzaldehyde levofloxacin hydrazone inducing the growth arrest and apoptosis of human hepatocarcinoma cells. Cancer Cell Int. 2013;13(1):1–10.

- Demirci A, Karayel K.G, Tatar E, Okullu S.Ö, Unübol N, Taşli P.N, et al. Synthesis and evaluation of novel 1,3,4-thiadiazole–fluoroquinolone hybrids as antibacterial, antituberculosis, and anticancer agents. Turkish J Chem. 2018;42(3):839–858.

- Mercorelli B. Design, Synthesis, and invitro Antibacterial Activity of Fluoroquinolone Derivatives Containing a Chiral 3-(Alkoxyimino)-2-(aminomethyl)azetidine Moiety. ChemMedChem. 2012;7(7):1230–1236.

- Sultana N, Arayne M.S, Rizvi S.B.S, Mesaik M.A. Synthesis, characterization and biological evaluation of a series of levofloxacin carboxamide analogues. Bull Korean Chem Soc. 2009;30(10):2294–2298.

- Zee S.H, Su H.P. A Convenient Method for the Preparation of Ellipticine. J Chinese Chem Soc. 1987;34(2):135–139.

- Mishra S, Dahima R. In-vitro ADME studies of TUG-891, a GPR-120 inhibitor using Swiss ADME predictor. J Drug Deliv Ther. 2019;9(3):661–668.

- Kanar M.A, Monther F.M, Ayad M.R. Molecular Docking study, and In vitro Evaluation of Antitumor Activity of Some New Isoxazoline and Pyrazoline Derivatives of Nabumetone against breast cancer cell line (MCF-7). Al Mustansiriyah J Pharm Sci. 2022;22(3):24–34.

- Marwa A.S, Karima F.A, Basma M.A. Synthesizing, Studying Molecular Docking, Characterizing, and Preliminary Evaluating Anti-Bacterial Effects of Derivatives of Serotonin Contain Imidazolidine Ring. Al Mustansiriyah J Pharm Sci. 2022;22(3):1–16.

- Caldwell G, Yan Z, Tang W, Dasgupta M, Hasting B. ADME Optimization and Toxicity Assessment in Early- and Late-Phase Drug Discovery. Curr Top Med Chem. 2009;9(11):965–680.

- Chen X, Li H, Tian L, Li Q, Luo J, Zhang Y. Analysis of the Physicochemical Properties of Acaricides Based on Lipinski’s Rule of Five. J Comput Biol. 2020;27(9):1397–1406.

- Adeniyi AA, Ajibade PA. Comparing the suitability of autodock, gold and glide for the docking and predicting the possible targets of Ru(II)-based complexes as anticancer agents. Molecules. 2013;18(4):3760–3778.

- Yasir F.M, Shakir M.A, Ayad K.K. Design, Molecular Docking, Synthesis of Aromatic Amino Acids Linked to Cephalexin. Al Mustansiriyah J Pharm Sci. 2022;21(3):25–34.