Applied Chemical Engineering

Synthesis, Characterisation and Application of New Amino Acid Proline Derivatives

Ameer Alaa Abdzaid

Department of Chemistry, College of Science, University of Babylon

Faris Hamood Mohammed

Department of Chemistry, College of Science, University of Babylon

Khudheyer Jawad Kadem

Department of Chemistry, College of Science, University of Babylon

DOI: https://doi.org/10.59429/ace.v9i1.5787

Keywords: Proline derivatives; Cephalexin; Sulfadiazine; 4-Amino antipyrine

---

Abstract

Five carrier drugs derived from proline were synthesised from proline 1 through an identical synthetic pathway: N-(carboxymethyl proline)-Ampicillin (A1), N-(carboxymethyl proline)-4-Amino antipyrine (A2), N-(carboxymethyl proline)-Cephalexin (A3), N-(carboxymethyl proline)-Ciprofloxacin (A4), and N-(carboxymethyl proline)-Sulfadiazine (A5). All intermediates and final products were identified using IR and 1H-NMR techniques. The antibacterial efficacy was assessed using the paper disc diffusion method. A strategy aimed at Gram-negative (Escherichia coli) and Gram-positive (Staphylococcus aureus) bacteria revealed that specific synthesised compounds demonstrated potential effectiveness against the evaluated pathogens compared to the commercially available antibiotic (Ampicillin). Molecular docking simulations were conducted for all synthesised compounds against DNA gyrase of Staphylococcus aureus and E. coli; the results indicated that the screened compounds possess potential activity for inhibiting DNA gyrase.

---

References

[1]. S. K. Kumar, M. (2024). Environment-friendly Simple, and Straight forward Approach Towards the C-4 functionalization of (2 S)-5-oxoproline Methyl Ester. Current Bioactive Compounds, 20(10), E260124226225.‏

[2]. E. M. Swiss, G. F., Neustadt, B. R., Gold, E. H., Sommer, J. A., Brown, A. D., ... & Baum, T. (1988). Synthesis and pharmacological activity of angiotensin-converting enzyme inhibitors: N-(mercaptoacyl)-4-substituted-(S)-prolines. Journal of medicinal chemistry, 31(4), 875-885.‏

[3]. Aubry, A., Cung, M. T., & Marraud, M. (1985). . beta. I and. beta. II-turn conformations in model dipeptides with the Pro-Xaa sequences. Journal of the American Chemical Society, 107(25), 7640-7647.‏

[4]. Y. R. Bhandari, J., Joshi, H., Thomson, S., Patel, V., & Mishra, R. (2021). Effect of Chronic Treatment with D2 Allosteric Modulator PAOPA on the Expression of Cerebral Dopamine Neurotrophic Factor (CDNF) in Select Brain Regions. International Journal of Peptide Research and Therapeutics, 27(4), 2551-2557.‏

[5]. Juaristi, E. (2023). The 2021 Nobel Prize in Chemistry: Relevance of Asymmetric Organocatalysis and Green Chemistry. 171,000 190M, 1.‏

[6]. Foster, A. J., van den Noort, M., & Poolman, B. (2024). Bacterial cell volume regulation and the importance of cyclic di-AMP. Microbiology and Molecular Biology Reviews, 88(2), e00181-23.‏

[7]. A. P. Young, V. G., & Johnson, R. L. (2005). Stereoselective Synthesis of α, α ‘-Biprolines. Organic letters, 7(1), 35-38.‏

[8]. Q. Li Y. Yang, C., Wu, W., Hai, J., & Li, X. (2024). Atroposelective synthesis of N–N axially chiral pyrrolyl (aza)-quinolinone by de novo ring formation. Organic Chemistry Frontiers, 11(3), 726-734.

[9]. A. W. (2018). Professor Krystyna Kotełko and her contribution to the study of Proteus endotoxin. Innate immunity, 24(3), 148-151.

[10]. Q. Li Y. Yang, C., Wu, W., Hai, J., & Li, X. (2024). Atroposelective synthesis of N–N axially chiral pyrrolyl (aza)-quinolinone by de novo ring formation. Organic Chemistry Frontiers, 11(3), 726-734.‏

[11]. M. Yu J. Blackmond, D. G. (2024). Kinetic Resolution as a General Approach to Enantioenrichment in Prebiotic Chemistry. Accounts of Chemical Research, 57(16), 2234-2244.

[12]. Zhang, C., Wang, T., Li, S., Lu, Z., Xu, M., Li, C., ... & Zhang, J. (2024). Adjusting the Coordination Configuration by Changing Electrostatic Potential: Introducing N/O/S Heteroatoms Based on the Electronic Effect. The Journal of Organic Chemistry, 89(23), 17567-17576.‏

[13]. Zhang, C., Wang, T., Li, S., Lu, Z., Xu, M., Li, C., ... & Zhang, J. (2024). Adjusting the Coordination Configuration by Changing Electrostatic Potential: Introducing N/O/S Heteroatoms Based on the Electronic Effect. The Journal of Organic Chemistry, 89(23), 17567-17576.‏

[14]. Danial, A. W., & Basset, R. A. (2024). Amelioration of NaCl stress on germination, growth, and nitrogen fixation of Vicia faba at isosmotic Na–Ca combinations and Rhizobium. Planta, 259(3), 69.‏

[15]. L. M. A. Brahimi, F. T., Belkhadem, F., Karmaoui, M., & Othman, A. A. (2022). Synthesis of some 2-substituted pyrrolidine alkaloid analogues: N-benzyl-2-(5-substituted 1, 3, 4-oxadiazolyl) pyrrolidine derivatives and pharmacological screening. Journal of Saudi Chemical Society, 26(3), 101448.‏

[16]. R. V. Aversa, R., Apicella, A., & Petrescu, F. I. (2019). Some Aspects of the Human Body's Hydraulics. OnLine Journal of Biological Sciences, 19(3), 159-185.‏

[17]. V. (2020). The Metal Triggered Self Assembly of Cell-Adhesive and Fluorinated Collagen Mimetic Peptides (Doctoral dissertation, Purdue University). ‏

[18]. M. Zhang, L., Zhang, W., Lin, Q., & Luo, S. (2024). Enantioselective transformations by “1+ x” synergistic catalysis with chiral primary amines. Accounts of Chemical Research, 57(10), 1523-1537.‏

[19]. Al-Momani, L. A., & Lataifeh, A. (2022). Asymmetric Aldol “Reaction in Water” Using Ferrocene-Amino Acid Conjugates. Industrial & Engineering Chemistry Research, 61(6), 2417-2424.‏

[20]. Chatwichien, J. (2016). The Design, Synthesis, and Biological Evaluation of Dimeric Β-Carbolines Based on the Structure of Neokauluamine and the Study of Manzamine A Dimerization Toward Neokauluamine (Doctoral dissertation, University of Pennsylvania).‏

[21]. Schöbel, J. H., Liang, W., Wöll, D., & Bolm, C. (2020). Mechanochemical synthesis of 1, 2, 6-thiadiazine 1-oxides from sulfonimidamides and the fluorescence properties of the products. The Journal of Organic Chemistry, 85(23), 15760-15766.‏

[22]. Poomsuk, N., Vilaivan, T., & Siriwong, K. (2018). Insights into the structural features and stability of peptide nucleic acid with a D-prolyl-2-aminocyclopentane carboxylic acid backbone that binds to DNA and RNA. Journal of Molecular Graphics and Modelling, 84, 36-42.‏

[23]. R. H. Guillermo, C., Alfonso, F. M., & Alberto, G. (2012). Water-Soluble Pendant Copolymers Bearing Proline and Permethylated β-Cyclodextrin: pH-Dependent Catalytic Nanoreactors.‏

[24]. Kamanna, K. (2021). Amino acids and peptides organocatalysts: A brief overview on its evolution and applications in organic asymmetric synthesis. Current Organocatalysis, 8(1), 126-146.‏

[25]. Meng, J., Chang, F., Su, Y., Liu, R., Cheng, T., & Liu, G. (2019). Switchable catalysts used to control Suzuki cross-coupling and aza–Michael addition/asymmetric transfer hydrogenation cascade reactions. Acs Catalysis, 9(9), 8693-8701.‏

[26]. D. J., R., Muir, V. J., Rendle, P. M., & Brimble, M. A. (2007). A comparative study of different glycosylation methods for the synthesis of d-mannopyranosides of Nα-fluorenylmethoxycarbonyl-trans-4-hydroxy-l-proline allyl ester. Carbohydrate research, 342(17), 2628-2634. ‏

[27]. Huang, P. W., Chang, J. M., & Horng, J. C. (2016). Effects of glycosylated (2 S, 4 R)-hydroxyproline on the stability and assembly of collagen triple helices. Amino acids, 48(12), 2765-2772.‏

[28]. Malinowska, M., Jarzyński, S., Pieczonka, A., Rachwalski, M., Leśniak, S., & Zawisza, A. (2020). Optically pure aziridin-2-yl methanols as readily available 1H NMR sensors for enantiodiscrimination of α-racemic carboxylic acids containing tertiary or quaternary stereogenic centers. The Journal of Organic Chemistry, 85(18), 11794-11801.‏

[29]. Feng, L., Gao, G., Zhao, H., Zheng, L., Wang, Y., Stavropoulos, P., ... & Zhang, J. (2018). Synthesis of Tripeptide Derivatives with Three Stereogenic Centers and Chiral Recognition Probed by Tetraaza Macrocyclic Chiral Solvating Agents Derived from d-Phenylalanine and (1 S, 2 S)-(+)-1, 2-Diaminocyclohexane via 1H NMR Spectroscopy. The Journal of organic chemistry, 83(22), 13874-13887.‏

[30]. T., Z. Yanpu, H., Zhenchang, G., Guijin, Z., Xue, B., ... & Kai, Z. (2017). Maleic Anhydride Labeling-Based Approach for Quantitative Proteomics and Successive Derivatization of Peptides.