Effect of dihydropyrrol and maleimide derivatives on the state of the liver and colon in normal rats and those with colorectal carcinogenesis induced by dimethylhydrazine

Kuznietsova, Halyna; Ov, Lynchak; Mo, Danylov; Ip, Kotliar; Vk, Rybal'chenko

doi:10.15407/ubj85.03.074

Cited by 18 publications

(13 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The proliferation of progenitor cells of colonocytes remains unaltered, intensity of the regenerating mucosa does not differ from physiological one. The findings indicate a fairly wide therapeutic window of D1, accordingly, its safety for the intestine, which is consistent with our previous data [11,12,14].…”

Section: Discussionsupporting

confidence: 93%

“…Medicinal products in this class include dihydropyrrole derivative 5-amino-4-(1,3-benzothiazole-2-yl)-1-(3-methoxyphenyl)-1,2-dihydro-3Н-pyrrol-3-one (D-1) іn silico synthesized at Research and Production Biochemical Center of Taras Shevchenko National University as targeted inhibitors of protein kinase, which due to the spatial structure of the molecule interacts with the ATP-binding centre of tyrosine protein kinases and is their effective blocker [7][8][9]. Since the cytotoxic effect of the medicinal product D1 has been demonstrated on the transformed lines [7,8,10] and cancer cells [11], it is said to be a potential compound for use in clinical practice [12][13][14].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Effect of Pyrrole Derivative on the Rat Colonic Mucosa Compared to 5-Fluorouracil

Yena

Dzyubenko

2016

EUREKA: Life Sciences

View full text Add to dashboard Cite

Prevention the development of malignant tumors and treatment of cancer patients remains an important problem today. In spite of substantive progress in the cancer diagnostics and treatment cancer occupies one of the main places in human morbidity and mortality in the World. Targeted therapy is an alternative to traditional one through targeted action on tumor cells and relatively low toxicity. Inhibitor of membrane tyrosine kinases dihydropyrrole derivative 5-amino-4-(1,3-benzothiazole-2-yl)-1-(3- methoxyphenyl)-1,2-dihydro-3Н-pyrrol-3-one (D-1) has significant antitumor activity on colorectal cancer and low toxicity acting in effective dose. However, to assess the D-1 therapeutic gap the investigation of its higher doses is necessary. The investigation was aimed at D-1 effects applied at different doses compared to 5-fluorouracil one on rats ascending colon mucosa. The research has found out that the dihydropyrrole derivative has no damaging effect on the colon of rats, whereas the administration of 5-fluorouracil causes marked mucosal lesion of the ascending colon. Hereby D-1 low toxicity to ascending colon mucosa compared to 5-FU and wide therapeutic gap of the first was concluded.

show abstract

Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Effect of Pyrrole Derivative on the Rat Colonic Mucosa Compared to 5-Fluorouracil

Yena

Dzyubenko

2016

EUREKA: Life Sciences

View full text Add to dashboard Cite

show abstract

“…Antitumor activity of the agent was also demonstrated on rat model of chemically induced colon cancer [10]. Moreover, MI-1 is relatively safe for the digestive, reproductive, and excretory systems under chronic exposure, as evidenced by [11–13]. Furthermore, when administered to rats experiencing colon cancer, MI-1 attenuates inflammation of mucosa, adjacent to colorectal tumors [10, 11].…”

Section: Introductionmentioning

confidence: 99%

“…Moreover, MI-1 is relatively safe for the digestive, reproductive, and excretory systems under chronic exposure, as evidenced by [11–13]. Furthermore, when administered to rats experiencing colon cancer, MI-1 attenuates inflammation of mucosa, adjacent to colorectal tumors [10, 11]. MI-1 also reveals antioxidant properties on CoCl 2 -induced oxidative stress model [14].…”

Section: Introductionmentioning

confidence: 99%

Anti-Inflammatory Effects of Protein Kinase Inhibitor Pyrrol Derivate

Kuznietsova

Yena

Kotlyar

et al. 2016

The Scientific World Journal

View full text Add to dashboard Cite

In our previous studies we showed antitumor and anti-inflammatory activities of protein kinases inhibitor pyrrol derivate 1-(4-Cl-benzyl)-3-Cl-4-(CF3-fenylamino)-1H-pyrrol-2,5-dione (MI-1) on rat colon cancer model. Therefore anti-inflammatory effect of MI-1 on rat acetic acid induced ulcerative colitis (UC) model was aimed to be discovered. The anti-inflammatory effects of MI-1 (2.7 mg/kg daily) compared to reference drug Prednisolone (0.7 mg/kg daily) after 14-day usage were evaluated on macro- and light microscopy levels and expressed in 21-grade scale. Redox status of bowel mucosa was also estimated. It was shown that in UC group the grade of total injury (GTI) was equal to 9.6 (GTIcontrol = 0). Increase of malonic dialdehyde (MDA) by 89% and protein carbonyl groups (PCG) by 60% and decrease of superoxide dismutase (SOD) by 40% were also observed. Prednisolone decreased GTI to 3 and leveled SOD activity, but MDA and PCG remained higher than control ones by 52% and 42%, respectively. MI-1 restored colon mucosa integrity and decreased mucosa inflammation down to GTI = 0.5 and leveled PCG and SOD. Thus, MI-1 possessed anti-inflammatory properties, which were more expressed that Prednisolone ones, as well as normalized mucosa redox balance, and so has a prospect for correction of inflammatory processes.

show abstract

“…Зменшення вмісту моноцитів у крові за умов застосування МІ-1 як у 5-, так і у 10-кратній дозах може бути пов'язаним із активним виходом цих клітин до тканин для участі у їх відновленні. Таке припущення базується на даних досліджень [18], у яких показано ознаки запалення і наявність дис-трофічних змін у таканинах шлунково-киш-кового тракту після впливу МІ-1. Препарат порівняння 5-ФУ у відповідній концентрації (дозі 8,6 мг/кг, яка ефективна) викликає змен-шення кількості лейкоцитів у крові (Р=0,001) із зменшенням вмісту нейтрофільних грану-лоцитів (Р=0,001), лімфоцитів (Р=0,001) і моноцитів (Р=0,002, див.…”

Section: результати та їх обговоренняunclassified

The Hematological Effects of the Protein Kinases Inhibitor Maleimide Derivative and 5 Fluorouracil

Byelinska¹,

Rybalchenko²,

Tsyvinska³

et al. 2017

Fiziol Zh

View full text Add to dashboard Cite

ВСТУПСтворення нових сполук з протипухлинною активністю і низькою токсичністю залиша-ється пріоритетним напрямком досліджень у біології і медицині. Одним із способів регуля-ції проліферативної активності є пригнічення функціонально активних ферментів-кіназ, які у пухлинних клітинах забезпечують їх виживання і неконтрольований поділ, за допомогою так званих цільових (таргетних) препаратів. Прикладом такої успішної ре-гуляції є застосування в клінічній практиці інгібіторів хімерної BCR/ABL-кінази імати-нібу [1] і бозутинібу [2] за умов хронічної мієлоїдної лейкемії, тирозинкінази Брутона -ібрутинібу [3] за хронічної лімфоцитарної лейкемії, Янус(Jak)-кіназ -руксолютинібу [4] за мієлопроліферативних захворювань тощо. Перевагами цих препаратів є їх висока ефек-тивність і низька токсичність. Але розвиток стійкості лейкемічних клітин до них [5,6] та висока вартість спонукає дослідників до пошуку нових сполук з аналогічною актив-ністю і доступністю для населення України.Похідне малеіміду (MІ-1, 1-(4-Cl-бензил)-3-Cl-4-(CF 3 -феніламіно)-1Н-пірол-2,5-діон) створено in silico і синтезовано на хіміч-ному факультеті Київського національного університету імені Тараса Шевченка як конкурентний інгібітор АТФ-зв'язувального сайту протеїнкіназ [7]. МI-1 in vitro інгібує

show abstract

Effect of dihydropyrrol and maleimide derivatives on the state of the liver and colon in normal rats and those with colorectal carcinogenesis induced by dimethylhydrazine

Cited by 18 publications

References 25 publications

Effect of Pyrrole Derivative on the Rat Colonic Mucosa Compared to 5-Fluorouracil

Effect of Pyrrole Derivative on the Rat Colonic Mucosa Compared to 5-Fluorouracil

Anti-Inflammatory Effects of Protein Kinase Inhibitor Pyrrol Derivate

The Hematological Effects of the Protein Kinases Inhibitor Maleimide Derivative and 5 Fluorouracil

Contact Info

Product

Resources

About