Different bonding of triazolopyrimidine to platinum(IV). Structural and in vitro cytotoxicity studies

Łakomska, Iwona; Jakubowski, Mateusz; Barwiołek, Magdalena; Muzioł, Tadeusz

doi:10.1016/j.poly.2018.12.022

Cited by 9 publications

(4 citation statements)

References 37 publications

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“…Most of the significant investigations with coordination compounds have been directed to the development of anti-tumor compounds of different metals [12] that could show improved therapeutic indexes and wider activity spectra. Such derivatives are interesting for their many biological effects such as antimicrobial [13,14], antitumor [15][16][17][18][19] and antiparasitic [20][21][22] activity.…”

Section: Introductionmentioning

confidence: 99%

Cytotoxic Activity of Organotin(IV) Derivatives with Triazolopyrimidine Containing Exocyclic Oxygen Atoms

et al. 2020

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In this study cytotoxicity of organotin(IV) compounds with 1,2,4-triazolo[1,5-a]pyrimidines, Me3Sn(5tpO) (1), n-Bu3Sn(5tpO) (2), Me3Sn(mtpO) (3), n-Bu3Sn(mtpO) (4), n-Bu3Sn(HtpO2) (5), Ph3Sn(HtpO2) (6) where 5HtpO = 4,5-dihydro-5-oxo-[1,2,4]triazolo-[1,5-a]pyrimidine, HmtpO = 4,7-dihydro-5-methyl-7-oxo-[1,2,4]triazolo-[1,5-a]pyrimidine, and H2tpO2 = 4,5,6,7-tetrahydro-5,7- dioxo-[1,2,4]triazolo-[1,5-a]-pyrimidine, was assessed on three different human tumor cell lines: HCT-116 (colorectal carcinoma), HepG2 (hepatocarcinoma) and MCF-7 (breast cancer). While 1 and 3 were inactive, compounds 2, 4, 5 and 6 inhibited the growth of the three tumor cell lines with IC50 values in the submicromolar range and showed high selectivity indexes towards the tumor cells (SI > 90). The mechanism of cell death triggered by the organotin(IV) derivatives, investigated on HCT-116 cells, was apoptotic, as evident from the externalization of phosphatidylserine to the cell surface, and occurred via the intrinsic pathway with fall of mitochondrial inner membrane potential and production of reactive oxygen species. While compound 6 arrested the cell progression in the G2/M cell cycle phase and increased p53 and p21 levels, compounds 2, 4 and 5 blocked cell duplication in the G1 phase without affecting the expression of either of the two tumor suppressor proteins. Compounds 1 and 2 were also investigated using single crystal X-ray diffraction and found to be, in both cases, coordination polymers forming 1 D chains based on metal-ligand interactions. Interestingly, for n-Bu3Sn(5tpO)(2) H-bonding interactions between 5tpO− ligands belonging to adjacent chains were also detected that resemble the “base-pairing” assembly and could be responsible for the higher biological activity compared to compound 1. In addition, they are the first example of bidentate N(3), O coordination for the 5HtpO ligand on two adjacent metal atoms.

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Section: Introductionmentioning

confidence: 99%

Cytotoxic Activity of Organotin(IV) Derivatives with Triazolopyrimidine Containing Exocyclic Oxygen Atoms

et al. 2020

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“…Moreover, design, and synthesis of the biologically potent nitrogen/oxygen containing heterocycles. copper(II) [61] ruthenium(III), [62] platinum(IV) [63] also reported recently as efficacious cytotoxic agents. More recently, Rangappa and co-workers described IBD-mediated synthesis (Yield = 90 %) and screening of various 1,2,4-triazolopyrimidine for cytotoxicity study (IC 50 , MCF = 3.91-93.8 μM; MDA-MB-231 = 50-100 μM) on human breast cancer cell lines.…”

Section: Introductionmentioning

confidence: 90%

“…Also the recent biological profile of 1,2,4‐triazolopyrimidine template endowed with outstanding biomedicinal activities such as antiherpetic, [48] LSD1/KDM1A, [49] PDE‐4B [50] and TDP2 inhibitors, [51] anti‐alzheimer agent, [52] antitrypanosomiasis, [53] antihyperglycemic, [54] antihypertensive, [26] antimicrobial, [55] anti‐epileptic, [56] anti‐microbaladenosine receptor antagonists, [57] antiproliferative, [58] microtubule stabilizing agents [59] and antitubercular [60] inveigle the consideration of medicinal chemists. Furthermore, 1,2,4‐triazolopyrimidine complexes with copper(II) [61] ruthenium(III), [62] platinum(IV) [63] also reported recently as efficacious cytotoxic agents. More recently, Rangappa and co‐workers described IBD‐mediated synthesis (Yield=90 %) and screening of various 1,2,4‐triazolopyrimidine for cytotoxicity study (IC 50 , MCF=3.91–93.8 μM; MDA‐MB‐231=50–100 μM) on human breast cancer cell lines [64] …”

Section: Introductionmentioning

confidence: 97%

Recent Synthetic and Biological Developments on 1,2,4‐Triazolopyrimidines

Kaushik,

Kumar,

Khokhar

et al. 2023

ChemistrySelect

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Abstract1,2,4‐Triazolopyrimidines scaffold spaciously acknowledged with anticancer, antimalarial, antitubercular and many other fascinating biological applications in recent years (2015–2022). Moreover, numerous mild synthetic methodologies reported, which has been summarized as (i) condensation of 2‐amino‐1,2,4‐triazole or 5‐amino‐1,2,4‐triazole with 1,3‐dielectrophilic equivalents like 1,3‐diketones, β‐ketoester (ii) oxidative‐cyclization of hydrazones or related analogues. This review would flourish the synthetic and medicinal chemist to design more bioactive 1,2,4‐triazolopyrimidines molecules for drug development with enhanced binding interactions, structural features with the help discussed SAR and cost effective methodologies in the coming years.

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“…The pyrimidine skeleton is the parent substance of many vital compounds that occur in nature, particularly in nucleobases of nucleic acids such as cytosine, thymine, and uracil. Moreover, pyrimidine scaffolds are readily accessible through the Biginelli reaction as well as possess a wide diversity of pharmacological and therapeutic properties including antimicrobial [ 1 ], antibacterial [ 2 ], antifungal [ 3 ], herbicidal activity [ 4 ], anti-inflammatory [ 5 ], therapeutic potentiality [ 6 ], antitubercular [ 7 ], anticancer [ 8 ], anticonvulsant [ 9 ], antileishmanial [ 10 ], antihypertensive [ 11 , 12 ], cytotoxicity [ 13 ], and antitumor [ 14 ]. Tarceva ® (Erlotinib) is one of the most often used pyrimidine-based anticancer medicines, as seen in Figure 1 .…”

Section: Introductionmentioning

confidence: 99%

Pyrimidines-Based Heterocyclic Compounds: Synthesis, Cytoxicity Evaluation and Molecular Docking

et al. 2022

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A variety of structurally different pyrimidines were synthesized. Elemental analysis, FT-IR, 1H NMR, and 13C NMR spectroscopy were used to confirm the chemical structures of all prepared compounds. The synthesized pyrimidines were screened against the growth of five human cancer cell lines (prostate carcinoma PC3, liver carcinoma HepG-2, human colon cancer HCT-116, human breast cancer MCF-7, human lung cancer A-549), and normal human lung fibroblasts (MRC-5) using MTT assay. Most of the screened pyrimidines have anti-proliferative activity on the growth of the PC3 cell line. Compounds 3b and 3d were more potent than the reference vinblastine sulfate (~2 to 3 × fold) and they can be considered promising leads for treating prostate cancer disease. Moreover, the screened compounds 3b, 3f, 3g, 3h, and 5 were assessed according to the values of their selectivity index (SI) and were found to be more selective and safer than vinblastine sulfate. Furthermore, using in silico computational tools, the physicochemical properties of all pyrimidine ligands were assessed, and the synthesized compounds fall within the criteria of RO5, thus having the potential to be orally bioavailable.

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Different bonding of triazolopyrimidine to platinum(IV). Structural and in vitro cytotoxicity studies

Cited by 9 publications

References 37 publications

Cytotoxic Activity of Organotin(IV) Derivatives with Triazolopyrimidine Containing Exocyclic Oxygen Atoms

Cytotoxic Activity of Organotin(IV) Derivatives with Triazolopyrimidine Containing Exocyclic Oxygen Atoms

Recent Synthetic and Biological Developments on 1,2,4‐Triazolopyrimidines

Pyrimidines-Based Heterocyclic Compounds: Synthesis, Cytoxicity Evaluation and Molecular Docking

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