Synthesis of Polypyridyl Palladium (Ⅱ) Complexes Modified with Morpholine Group and Its Antibacterial Activity Anti-Staphylococcus Aureus

Abstract

Abstract: One Polypyridyl Pd(Ⅱ) complex (Pd1) containing modified morpholine group was synthesized from 4’-[4-(4-morpholinobutyloxy) phenyl]-2,2’∶6’,2’-tripyridine and characterized by ¹H NMR, element analysis and single crystal X-ray diffraction. The antibacterial activity of Pd1 was investigated against S. aureus with the MIC (minimum inhibition concentration) value of 62.48 μg/mL and the effect of Pd1 complex on S. aureus growth was investigated by growth curves. Bacteria resistance development assay indicate that the S. aureus cannot easily develop drug-resistance to Pd1. In addition, Pd1 complex can strengthen the susceptibility of S. aureus to clidamycin hydrochloride when it is combined with clidamycin hydrochloride. Meanwhile, Pd1 has a significant inhibitory effect on biofilms related to drug resistance, and show obviously inhibitory activity against the toxins from S. aureus.

Key words: metal complex, polypyridine palladium complex, morpholine, crystal structure, anti-Staphylococcus aureus, antibiotic combination

CLC Number:

O641

WANG Runbin, HAN Tianzhi, LI Zhimin, YAO Zhiling, LIAO Xiangwen, WANG Jintao. Synthesis of Polypyridyl Palladium (Ⅱ) Complexes Modified with Morpholine Group and Its Antibacterial Activity Anti-Staphylococcus Aureus[J]. Journal of Synthetic Crystals, 2023, 52(10): 1842-1849.

References

[1] WERTHEIM H F, MELLES D C, VOS M C, et al. The role of nasal carriage in Staphylococcus aureus infections[J]. The Lancet Infectious Diseases, 2005, 5(12): 751-762.
[2] GRUNDMANN H, AIRES-DE-SOUSA M, BOYCE J, et al. Emergence and resurgence of meticillin-resistant Staphylococcus aureus as a public-health threat[J]. The Lancet, 2006, 368(9538): 874-885.
[3] DE KRAKER M E A, STEWARDSON A J, HARBARTH S. Will 10 million people die a year due to antimicrobial resistance by 2050?[J]. PLoS Medicine, 2016, 13(11): e1002184.
[4] FREI A. Metal complexes, an untapped source of antibiotic potential?[J]. Antibiotics, 2020, 9(2): 90.
[5] HIJAZI S, VISAGGIO D, PIROLO M, et al. Antimicrobial activity of gallium compounds on ESKAPE pathogens[J]. Frontiers in Cellular and Infection Microbiology, 2018, 8: 316.
[6] CHOI S R, BRITIGAN B E, NARAYANASAMY P. Dual inhibition of Klebsiella pneumoniae and Pseudomonas aeruginosa iron metabolism using gallium porphyrin and gallium nitrate[J]. ACS Infectious Diseases, 2019, 5(9): 1559-1569.
[7] CHOI S R, SWITZER B, BRITIGAN B E, et al. Gallium porphyrin and gallium nitrate synergistically inhibit Mycobacterial species by targeting different aspects of iron/heme metabolism[J]. ACS Infectious Diseases, 2020, 6(10): 2582-2591.
[8] PIATEK M, GRIFFITH D M, KAVANAGH K. Quantitative proteomic reveals gallium maltolate induces an iron-limited stress response and reduced quorum-sensing in Pseudomonas aeruginosa[J]. JBIC Journal of Biological Inorganic Chemistry, 2020, 25(8): 1153-1165.
[9] KESAVAN M P, VINOTH KUMAR G G, DHAVEETHU RAJA J, et al. DNA interaction, antimicrobial, antioxidant and anticancer studies on Cu(Ⅱ) complexes of Luotonin A[J]. Journal of Photochemistry and Photobiology B: Biology, 2017, 167: 20-28.
[10] ŁODYGA-CHRUSCIŃSKA E, PILO M, ZUCCA A, et al. Physicochemical, antioxidant, DNA cleaving properties and antimicrobial activity of fisetin-copper chelates[J]. Journal of Inorganic Biochemistry, 2018, 180: 101-118.
[11] LIAO X W, JIANG G J, WANG J T, et al. Two ruthenium polypyridyl complexes functionalized with thiophen: synthesis and antibacterial activity against Staphylococcus aureus[J]. New Journal of Chemistry, 2020, 44(40): 17215-17221.
[12] LI F F, COLLINS J G, KEENE F R. Ruthenium complexes as antimicrobial agents[J]. Chemical Society Reviews, 2015, 44(8): 2529-2542.
[13] BOUBAKRI L, MANSOUR L, HARRATH A H, et al. N-Heterocyclic carbene-Pd(Ⅱ)-PPh₃ complexes as a new highly efficient catalyst system for the Sonogashira cross-coupling reaction: synthesis, characterization and biological activities[J]. Journal of Coordination Chemistry, 2018, 71(2): 183-199.
[14] AL-GHORBANI M, BUSHRA B A, ZABIULLA, et al. Piperazine and morpholine: synthetic preview and pharmaceutical applications[J]. Research Journal of Pharmacy and Technology, 2015, 8(5): 611.
[15] NAIM M J, ALAM O, ALAM M J, et al. A review on pharmacological profile of morpholine derivatives[J]. Journal of Pharmacy Pharmacology, 2015, 3(1): 40-51.
[16] RUPAK K, VULICHI S R, SUMAN K. Emphasizing morpholine and its derivatives (maid): a typical candidate of pharmaceutical importance[J]. International Journal of Chemical Sciences, 2016, 14: 1777-1788.
[17] ARSHAD F, KHAN M F, AKHTAR W, et al. Revealing quinquennial journey of morpholine: a SAR based review[J]. European Journal of Medicinal Chemistry, 2019, 167: 324-356.
[18] DARABI F, HADADZADEH H, SIMPSON J, et al. A water-soluble Pd(ii) complex with a terpyridine ligand: experimental and molecular modeling studies of the interaction with DNA and BSA; and in vitro cytotoxicity investigations against five human cancer cell lines[J]. New Journal of Chemistry, 2016, 40(11): 9081-9097.
[19] CHAI K K, JIANG Y H, HAN T Z, et al. Synthesis, characterization, DNA binding, topoisomerase I inhibition, and antiproliferation activities of (di-tert-butylbipyridine) platinum(Ⅱ) complexes[J]. Transition Metal Chemistry, 2018, 43(8): 657-664.
[20] LIU J Y, LI H X, LI H Z, et al. Rational design of dipicolylamine-containing carbazole amphiphiles combined with Zn²⁺ as potent broad-spectrum antibacterial agents with a membrane-disruptive mechanism[J]. Journal of Medicinal Chemistry, 2021, 64(14): 10429-10444.
[21] SHELDRICK G M. Crystal structure refinement with SHELXL[J]. Acta Crystallographica Section C, Structural Chemistry, 2015, 71(1): 3-8.
[22] COSTERTON J W. Introduction to biofilm[J]. International Journal of Antimicrobial Agents, 1999, 11(3/4): 217-221.
[23] GOLEIJ Z, MAHMOODZADEH HOSSEINI H, AMIN M, et al. Prokaryotic toxins provoke different types of cell deaths in the eukaryotic cells[J]. Toxin Reviews, 2017: 1-15.
[24] MARTINEZ-IRUJO J J, VILLAHERMOSA M L, ALBERDI E, et al. A checkerboard method to evaluate interactions between drugs[J]. Biochemical Pharmacology, 1996, 51(5): 635-644.