Cytotoxicity activity, in silico molecular docking, protein- and DNA-binding study of a new Ni(II) Schiff base complex

Biswas, Niladri; Khanra, Sumit; Sarkar, Arnab; Bhattacharjee, Shamee; Mandal, Deba Prasad; Chaudhuri, Ankur; Chakraborty, Sibani; Choudhury, Chirantan Roy

doi:10.1080/00958972.2018.1492118

Cited by 16 publications

(11 citation statements)

References 94 publications

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“…The ambient temperature X-ray structure of Ni(PrPyrr) has been previously described. [66] The novel low temperature X-ray structures of Pd(PrPyrr) and PdCl(HPrPyrr) delineated here are shown in Figure 3. Pd(PrPyrr) crystallized in the space group P21/c (Table S1, Figure S15) and is structurally similar to the room temperature X-ray structure of the compound (Figure S16).…”

Section: X-ray Structures Of Pd(prpyrr) and Pdcl(hprpyrr)mentioning

confidence: 95%

“…Modified literature methods were used to metalate H2PrPyrr with Ni II [66] and Pt II . [67] For Pt(PrPyrr), simply stirring the solution of the free ligand with K2[PtCl4] and sodium acetate in a binary mixture of DMSO-acetonitrile (50%, V/V) for 4 days at ambient temperature (as opposed to the 4-h reaction at 80 °C in DMF employed for the cyclohexyl-bridged ligand [67] ) afforded the product cleanly without formation of metal-containing by-products.…”

Section: Metal Chelate Synthesismentioning

confidence: 99%

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Complexities of the interaction of Ni(II), Pd(II) and Pt(II) pyrrole-imine chelates with human serum albumin

Sookai

Munro

2023

Preprint

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Human serum albumin (HSA) efficiently transports drugs in vivo: most are organic. Here, HSA binding affinity and site specificity are shown to depend on the identity of the d8 metal ion in Ni(II), Pd(II) and Pt(II) chelates of the bis(pyrrole-imine) ligand H2PrPyrr. Fluorescence quenching data for native and probe-bound HSA showed sites close to Trp-214 (subdomain IIA) are targeted. The Stern-Volmer constants, KSV, ranged from 10^4 M^(-1) to 10^5 M^(-1) while the affinity constants, Ka, ranged from 3.5 x 10^3 M^(-1) to 1 x 10^6 M^(-1) at 37 degrees Centigrade, following the order Pd(PrPyrr) > Pt(PrPyrr) > Ni(PrPyrr) > H2PrPyrr. Ligand uptake is enthalpically driven, hinging mainly on London dispersion forces. Induced CD spectra for the protein-bound ligands could be simulated by hybrid QM:MM TD-DFT methods, proving that the metal chelates neither decompose nor demetallate after uptake by HSA. Transport and delivery of the metal chelates by HSA in vivo could therefore be feasible.

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Section: X-ray Structures Of Pd(prpyrr) and Pdcl(hprpyrr)mentioning

confidence: 95%

Section: Metal Chelate Synthesismentioning

confidence: 99%

Complexities of the interaction of Ni(II), Pd(II) and Pt(II) pyrrole-imine chelates with human serum albumin

Sookai

Munro

2023

Preprint

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“…The ambient temperature X-ray structure of Ni(PrPyrr) has been previously described. 64 The novel low temperature X-ray structures of Pd(PrPyrr) and PdCl(HPrPyrr) delineated here are shown in Fig. 3.…”

Section: X-ray Crystal Structuresmentioning

confidence: 90%

“…Modified literature methods were used to metalate H2PrPyrr with Ni(II) 64 and Pt(II). 65 For Pt(PrPyrr), we found that simply stirring the solution of the free ligand with K2[PtCl4] and sodium acetate in a binary mixture of DMSO-acetonitrile (50%, V/V) for 4 days at ambient temperature (as opposed to the 4-h reaction at 80 C in DMF employed for the cyclohexyl-bridged ligand 65 ) afforded the product cleanly without significant formation of metal-containing by-products.…”

Section: Metal Chelate Synthesismentioning

confidence: 99%

Complexities of the interaction of Ni(II), Pd(II) and Pt(II) pyrrole-imine chelates with human serum albumin

Sookai

Munro

2022

Preprint

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Human serum albumin (HSA) is the most abundant blood protein and is responsible for the transport of many exogenous compounds, including clinically deployed and investigational drugs: most are organic. Here, Ni(II), Pd(II) and Pt(II) chelates of a tetradentate bis(pyrrole-imine) ligand, H2PrPyrr, were used to delineate how the identity of the d8 metal ion impacts the compound’s affinity for HSA. Fluorescence quenching data acquired on the native protein and HSA bound to site-specific probes showed the compounds target sites close enough to its single Trp-214 residue (subdomain IIA) to quench the fluorophore. The bimolecular quenching rate constants, k_q, were of the order of 10^1 to 10^4 times higher than the maximum diffusion-controlled collision constant of a biomolecule in water (10^10 M-1 s-1), reflecting a static fluorescence quenching mechanism. The Stern-Volmer constants, K_SV, spanned the range 10^4 M-1 to 10^6 M-1 at 37 oC, while the affinity constants, K_a, ranged from ~3 x 10^3 M-1 to ~8 x 10^7 M–1 at 37 oC, and followed the order Pd(PrPyrr) >> Pt(PrPyrr) > Ni(PrPyrr) > H2PrPyrr. The thermodynamics reflect enthalpically driven ligand uptake, hinging mainly on London dispersion forces (metal ion dependent), along with general multi-site binding. Notably, two reactive species exist for the Pd(II) system, affording the complex HSA•{Pda}{Pdb}. Molecular docking simulations (GLIDE XP) support the spectroscopic data, confirming that all ligands can target multiple binding sites in silico—all within ~20 Å of Trp-214. Although far- and near-UV CD spectroscopy indicated that the optically inactive ligands negligibly perturb the secondary and tertiary structure of HSA, substantial induced CD (ICD) spectra were recorded for the protein-bound ligands and could be simulated by hybrid QM:MM TD-DFT methods. This study highlights how appropriately chelated square planar d8 metal ions neither decompose nor demetallate after uptake by HSA, proving that metallodrug transport and delivery by HSA might be more feasible than generally acknowledged.

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“…The pyrrole structure is found in many therapeutic active compounds, including antitumors, antibiotics, anti-inflammatories, fungicides, and many drugs with antiproliferative effects. [89][90][91][92][93][94] Based on these findings, two Schiff bases containing a pyrrole ring and benzene derivatives were synthesized, and ADME/Tox profiling was performed, as well as interaction with PLK1 (Serinel/Threonine-Protein Kinase, also known as Polo-Like Kinase 1).…”

Section: Introductionmentioning

confidence: 99%

Pyrrole‐Based Schiff‐Bases: Synthesis, Fluorescent Properties, Molecular Docking and in silico ADME/Tox Profiling Studies

Özcan

2023

ChemistrySelect

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Condensation reactions of methyl 5‐formyl‐1H‐pyrrole‐2‐carboxylate with 4‐aminobenzonitrile and N, N‐dimethyl‐p‐phenylenediamine yielded two conjugated Schiff bases with pyrrole rings. Fluorescence spectroscopy was used to examine the molecules′ selectivity for different metal salts, and it was discovered that the PL1 molecule was selective for the Pb2+ ion. In addition, the interactions of the same molecules with the polo‐like kinase 1 (PLK1) enzyme were investigated by molecular docking with the Autock Tools 1.5.6 program, and the synthesized Schiff bases formed stable complexes with the PLK1 with binding affinity values of −6.5 and −6.4 kcal/mol for PL1 and PL2 respectively. The SwissADME and ADMET web tools were used to calculate in silico ADME/Tox profiles of the synthesized molecules.

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Cytotoxicity activity, in silico molecular docking, protein- and DNA-binding study of a new Ni(II) Schiff base complex

Cited by 16 publications

References 94 publications

Complexities of the interaction of Ni(II), Pd(II) and Pt(II) pyrrole-imine chelates with human serum albumin

Complexities of the interaction of Ni(II), Pd(II) and Pt(II) pyrrole-imine chelates with human serum albumin

Complexities of the interaction of Ni(II), Pd(II) and Pt(II) pyrrole-imine chelates with human serum albumin

Pyrrole‐Based Schiff‐Bases: Synthesis, Fluorescent Properties, Molecular Docking and in silico ADME/Tox Profiling Studies

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