Derivatives of diphosphonic acids: synthesis and biological activity

Zolotukhina, M. M.; Krutikov, V. I.; Lavrent'ev, A. N.

doi:10.1070/rc1993v062n07abeh000038

Cited by 26 publications

(9 citation statements)

References 28 publications

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“…Nevertheless, searching for new compounds with antineoplastic action continues to eliminate the serious side effects, to improve the clinical efficacy and to broaden the antitumor spectrum. In particular, palladium(II) bisphosphonates are promising species for the treatment of bone cancer and metastases: complexes include a cytotoxic metal (palladium) and a bisphosphonic acid, which possesses affinity for bone tissue and can ensure targeted delivery of the cytotoxic metal to the lesion site [2][3][4][5][6][7][8][9]. The P-C-P moiety present in bisphospho nic acids provides their active link to the bone matrix, and two side substituents determine their physicochemical and pharmacologic properties.…”

Section: P Nmr Spectroscopy Cytotoxic Activity (Ic 50 Based On Metalmentioning

confidence: 99%

Complexes of palladium(II) with 1-phenyl-1-hydroxymethylene bisphosphoniс acid and their antitumor activity

Kozachkova¹,

Tsaryk²,

TRACHEVSKYI³

et al. 2017

Ukr.Biochem.J.

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complex formation of K 2 [Pdcl 4 ] with 1-phenyl-1-hydroxymethylene bisphosphonic acid (PhhMBP, h 4 K e y w o r d s: palladium(II) complexes, bisphosphonic acid, cytotoxic activity, toxicity.C isplatin is still one of the most famous and efficient anticancer drugs used in the clinical practice [1]. Nevertheless, searching for new compounds with antineoplastic action continues to eliminate the serious side effects, to improve the clinical efficacy and to broaden the antitumor spectrum. In particular, palladium(II) bisphosphonates are promising species for the treatment of bone cancer and metastases: complexes include a cytotoxic metal (palladium) and a bisphosphonic acid, which possesses affinity for bone tissue and can ensure targeted delivery of the cytotoxic metal to the lesion site [2][3][4][5][6][7][8][9]. The P-C-P moiety present in bisphospho nic acids provides their active link to the bone matrix, and two side substituents determine their physicochemical and pharmacologic properties. To study the effect of the structure of complex and chemical nature of the substituents bonded to the carbon atom of bisphosphonate moiety on the biological activity, the formation of palladium(II) complexes with 1-phenyl-1-hydroxymethylene bisphosphoniс acid was investigated, which, besides two phosphonic groups, contain a hydroxy group and a phenyl moiety.

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Section: P Nmr Spectroscopy Cytotoxic Activity (Ic 50 Based On Metalmentioning

confidence: 99%

Complexes of palladium(II) with 1-phenyl-1-hydroxymethylene bisphosphoniс acid and their antitumor activity

Kozachkova¹,

Tsaryk²,

TRACHEVSKYI³

et al. 2017

Ukr.Biochem.J.

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“…As the antitumor drug, we used coordination compounds combining a cytostatic (the palladium ion) and MDP, which, being a structural analog of pyrophosphate, can deliver the cytostatic to the tumor in a targeted fashion [18]. The coordination environment of palladium in the complexes is formed by two oxygen atoms of the two phosphonic groups of the ligands plus two chloride ions [19]:…”

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confidence: 99%

Infrared Spectroscopy in Cancer Diagnosis and Chemotherapy Monitoring

et al. 2014

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We demonstrate that IR spectroscopic analysis can be used in diagnosis and chemotherapy monitoring for cancers of various organs at the molecular level. We used Fourier transform IR spectroscopy to study human breast and thyroid tumor tissues which were removed during surgery. The characteristic frequencies of C=O stretching vibrations in the IR spectra of tissues of pathological foci were compared with data from histological examination. In the IR spectra of healthy tissues or for benign tumors, the most intense absorption bands ν(C=O) are located in the interval 1675-1650 cm -1 . When malignant neoplasms are present in the organs, the intensity of the bands in this range of the spectrum is reduced, while the intensities of the absorption bands in the 1710-1680 cm -1 interval increase. We also studied lung tissue for mice of the C 57 B1/6 line for healthy tissue and after implantation of B-16 melanoma tumor. The IR spectra of healthy mouse lung tissue and mouse lung tissue with B-16 melanoma metastases in the region of the C=O stretching vibrations display the same differences. We found that when lung malignancy was treated with the optimal dose of a synthesized drug based on palladium complexes of methylenediphosphonic acid, the spectroscopic signs of the presence of metastases in the lungs disappear, and the IR spectrum of the lung tissue after treatment practically coincides with the spectrum of healthy lung tissue.Introduction. In connection with the steady trend of increasing illness and death from malignant neoplasms, an important problem in modern science and medicine is prevention, diagnosis, and treatment of such diseases. Diagnosis of malignant neoplasms is a very complicated area in oncology, since tumors do not always result in specifi c clinical symptoms, especially in the early stages [1, 2]. Vibrational spectroscopy methods, which detect malignancy in organs at the level of vibrations of molecular fragments [3][4][5][6][7][8][9][10][11][12][13][14], are promising for this avenue of study. Information obtained by IR and Raman spectroscopy methods can reveal, at the molecular level, special features of malignancy which in the early stages of tumor development are not apparent in the cell structure or cause problems for proper verifi cation of the tumor process. However, to date no universal signs have been observed by these methods in the IR and Raman spectra which unambiguously, consistently, and reliably determine the presence of malignancy in various human and animal organs.In treatment of cancers, the best effect is achieved when combining surgical methods, radiation, and chemotherapy [15]. The main task of chemotherapy is targeted delivery of a low-toxicity therapeutic substrate to the organ attacked by the disease. Development of methods for synthesis of new low-toxicity compounds meeting these requirements is needed. In addition to identifi cation of universal spectroscopic signs of the presence of malignancy in the organs, there is also scientifi c and practical interest in the use of IR spe...

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confidence: 99%

“…A fragment of phosphonous acid combined with an aminoalkyl group underlies the structure of a series of organic compounds endowed with a high biological activity without high toxicity, and also anticorrosion properties with respect to carbon and low-alloy steels [1][2][3][4].…”

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Synthesis of (pyrrolidin-1-yl- and morpholinoalkyl)phosphonic acids

2009

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A fragment of phosphonous acid combined with an aminoalkyl group underlies the structure of a series of organic compounds endowed with a high biological activity without high toxicity, and also anticorrosion properties with respect to carbon and low-alloy steels [1][2][3][4].Convenient synthons for introduction of this fragment are phosphonic acid and its esters whose aminoalkylation provided a wide series of nitrogen-containing phosphonous acids, also with nitrogen heterocyclic substituents involved into the composition of the amino component in the condensation reaction and linked to the reacting primary amino group through an amino-hydrocarbon bridge [5]. Although in patent [5] in the general claim was declared a possibility to synthesize N-heterylalkylphos-phonic acids where the heterocyclic nitrogen is linked to the phosphonic group through a single-carbon bridge (at m = 0), these compounds, e.g., with a pyrrolidine or morpholine fragments were not described in the given examples, and their properties were not characterized. Moreover the reactivity of secondary alicyclic amines can considerably differ from that of primarily linear ana-logs. It is known that the appearance of steric hindrances at the secondary nitrogen in the amine component considerably reduces its reactivity and the acid properties of the resulting aminoalkylphosphonic acids [6].Ht(CH 2 CH 2 NH n ) m [CR 1 R 2 P=O(OH) 2 ] p Mannich reaction using formaldehyde, acetone, or methyl ethyl ketone as carbonyl component. n = 0, 1; m = 0-3; p = 1, 2.In this study we perfomed the aminoalkylation of phosphonic acid with pyrrolidine and morpholine along R 1 = R 2 = H (a), CH 3 (b); R 1 = CH 3 , R 2 = C 2 H 5 (c); No X (I, III), X = O (II, IV).It turned out that at employing the mentioned amines the plausible yields (50-85%) of the target products were attained only at a prolonged heating of the reaction mixture for 10-12 h.The synthesized compounds IIIa-IIIc, IVa, and IVb are lightly colored oily substances, well soluble in water and poorly soluble in organic solvents. Like all known aminoalkylphosphonic acids [6, 7] the obtained compounds exist in solution in zwitter-ionic betaine-like structure A.This fact is confirmed by the downfield shift by 0.2-0.5 ppm of the signals of methylene protons in the 1 H NMR spectra as compared to the analogous signals

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Derivatives of diphosphonic acids: synthesis and biological activity

Cited by 26 publications

References 28 publications

Complexes of palladium(II) with 1-phenyl-1-hydroxymethylene bisphosphoniс acid and their antitumor activity

Complexes of palladium(II) with 1-phenyl-1-hydroxymethylene bisphosphoniс acid and their antitumor activity

Infrared Spectroscopy in Cancer Diagnosis and Chemotherapy Monitoring

Synthesis of (pyrrolidin-1-yl- and morpholinoalkyl)phosphonic acids

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