Synthesis, characterisation and in vitro cytotoxicity studies of a series of chiral platinum(II) complexes based on the 2-aminomethylpyrrolidine ligand: X-ray crystal structure of [PtCl2(R-dimepyrr)] (R-dimepyrr=N-dimethyl-2(R)-aminomethylpyrrolidine)

Lamivudine (3TC) and zidovudine (AZT) are antiviral agents used to manage HIV/AIDS infection. The compounds require frequent dosing, exhibit unpredictable bioavailability and a side effect profile that includes hepato- and haema-toxicity. A novel pseudo one-solvent bottom-up approach and Design of Experiments using sodium dodecyl sulphate (SDS) and α-tocopheryl polyethylene glycol succinate 1000 (TPGS 1000) to electrosterically stablize the nano co-crystals was used to develop, produce and optimize 3TC and AZT nano co-crystals. Equimolar solutions of 3TC in surfactant dissolved in de-ionised water and AZT in methanol were rapidly injected into a vessel and sonicated at 4 °C. The resultant suspensions were characterized using a Zetasizer and the particle size, polydispersity index and Zeta potential determined. Optimization of the nanosuspensions was conducted using a Central Composite Design to produce nano co-crystals with specific identified and desirable Critical Quality Attributes including particle size (PS) < 1000 nm, polydispersity index (PDI) < 0.500 and Zeta potential (ZP) < −30mV. Further characterization was undertaken using Fourier Transform infrared spectroscopy, energy dispersive X-ray spectroscopy, differential scanning calorimetry, powder X-ray diffraction and transmission electron microscopy. In vitro cytotoxicity studies revealed that the optimized nano co-crystals reduced the toxicity of AZT and 3TC to HeLa cells.

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Mixed natural arylolefin–quinoline platinum(II) complexes: synthesis, structural characterization and in vitro cytotoxicity studies

Acta Crystallographica Section C Structural Chemistry ◽

10.1107/s2053229618015978 ◽

2018 ◽

Vol 74 (12) ◽

pp. 1732-1743

Author(s):

Nguyen Thi Thanh Chi ◽

Pham Van Thong ◽

Truong Thi Cam Mai ◽

Luc Van Meervelt

Keyword(s):

Double Bond ◽

Cytotoxic Effect ◽

In Vitro Cytotoxicity ◽

Quinoline Derivative ◽

X Ray Diffraction ◽

Hep G2 ◽

X Ray ◽

Cytotoxicity Studies ◽

Mcf 7

Five new platinum(II) complexes bearing a eugenol and a quinoline derivative, namely [η2-4-allyl-2-methoxy-1-(propoxycarbonylmethoxy)benzene]-trans-dichlorido(quinoline-κN)platinum(II), [PtCl2(C15H20O4)(C9H7N)], (2), {η2-4-allyl-2-methoxy-1-[(propan-2-yloxy)carbonylmethoxy]benzene}-trans-dichlorido(quinoline-κN)platinum(II), [PtCl2(C15H19O4)(C9H7N)], (3), [η2-4-allyl-2-methoxy-1-(propoxycarbonylmethoxy)benzene]chlorido(quinolin-8-olato-κ2 N,O)platinum(II), [Pt(C9H6NO)Cl(C15H20O4)], (4), {η2-4-allyl-2-methoxy-1-[(propan-2-yloxy)carbonylmethoxy]benzene}chlorido(quinolin-8-olato-κ2 N,O)platinum(II), [Pt(C9H6NO)Cl(C15H20O4)], (5), and [η2-4-allyl-2-methoxy-1-(propoxycarbonylmethoxy)benzene]chlorido(quinolin-2-carboxylato-κ2 N,O)platinum(II), [Pt(C10H6NO2)Cl(C15H20O4)], (6), have been synthesized and fully characterized spectroscopically. A single-crystal X-ray diffraction study was carried out for complexes (2) and (4)–(6). PrEug [or 4-allyl-2-methoxy-1-(propoxycarbonylmethoxy)benzene] in (2), (4) and (6), and iPrEug (the propan-2-yloxy analogue of PrEug) in (3) and (5) coordinate with PtII at the ethylenic double bond of the allyl group. In (2)–(6), the donor N atom of the amine group occupies a trans position with respect to the double bond. A comparison of the IC50 values of 0.38–29.23 µM for (2)–(6) with cisplatin, as well as other platinum(II) complexes, indicates an excellent in vitro cytotoxicity against the KB, LU, Hep-G2 and MCF-7 cancer cell lines, with the highest cytotoxic effect (IC50 = 0.38–1.99 µM) being for complexes (4) and (5) bearing a quinolin-8-olate ligand.

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