Synthesis and antiproliferative activity evaluation of steroidal imidazo[1,2-a]pyridines

Rassokhina, Irina V.; Volkova, Yu. A.; Kozlov, Andrey S.; Scherbakov, Alexander M.; Andreeva, Olga E.; Ширинян, Валерий З.; Заварзин, И. В.

doi:10.1016/j.steroids.2016.06.001

Cited by 40 publications

(19 citation statements)

References 42 publications

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“…In this work, for the first time, as far as we know, the activity of ten newly synthesized imidazoheterocycles on the JEG-3 cell line was examined. Previous studies have examined a series of different derivatives but only in the breast cancer and prostate cancer cell line (RASSOKHINA et al, 2016). The cytotoxic effect was demonstrated only on the MCF-7 breast cancer cell line at the micromolar level.…”

Section: Resultsmentioning

confidence: 99%

Investigation of the effect of steroidal imidazoheterocycles hormone derivatives on JEG-3 trophoblast cells of choriocarcinoma

Todosijević¹,

Scherbakov²,

Volkova³

et al. 2021

Kragujevac J Science

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This study aimed to examine the biological activities of unique steroid hormone derivatives-steroidal imidazoheterocycles. The activity synthesized steroidal compounds were tested for the viability of JEG-3 trophoblast cells of choriocarcinoma. The results of the MTT cytotoxicity test showed that most of the examined steroidal imidazoheterocycles act proliferatively on the JEG-3 cell line, except (E, F, and J). Antiproliferative activity of these derivates is probably influenced by different substituents at position 17-C atom in the chemical structure of the hormone and by different substituents on the oxygen atom of acetamide group in the hormone molecule. In order to better confirm the antiproliferative activity of these derivatives, it is necessary to performed complex research on a large panel of cancer cell lines and by different assay.

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Section: Resultsmentioning

confidence: 99%

Investigation of the effect of steroidal imidazoheterocycles hormone derivatives on JEG-3 trophoblast cells of choriocarcinoma

Todosijević¹,

Scherbakov²,

Volkova³

et al. 2021

Kragujevac J Science

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“…In fulvestrant, the alkylsulfinyl moiety is attached to the endogenous estrogen receptor ligand, 17β-estradiol, at the 7-position, providing a structure similar to that of natural hormones but showing reverse biological activity. Recently, we have demonstrated that the modification of 17β-estradiol with imidazo[1,2-a]pyridine pendant at the 17α-position has the same effect (Rassokhina et al, 2016 ). 17α-Imidazopyridine-17β-methoxyestradiol showed remarkable effects as a selective ERα receptor modulator.…”

Section: Introductionmentioning

confidence: 95%

Steroidal Pyrimidines and Dihydrotriazines as Novel Classes of Anticancer Agents against Hormone-Dependent Breast Cancer Cells

et al. 2018

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Most breast and prostate tumors are hormone-dependent, making it possible to use hormone therapy in patients with these tumors. The design of effective endocrine drugs that block the growth of tumors and have no severe side effects is a challenge. Thereupon, synthetic steroids are promising therapeutic drugs for the treatment of diseases such as hormone-dependent breast and prostate cancers. Here, we describe novel series of steroidal pyrimidines and dihydrotriazines with anticancer activities. A flexible approach to unknown pyrimidine and dihydrotriazine derivatives of steroids with selective control of the heterocyclization pattern is disclosed. A number of 18-nor-5α-androsta-2,13-diene[3,2-d]pyrimidine, androsta-2-ene[3,2-d]pyrimidine, Δ1, 3, 5(10)-estratrieno[16,17-d]pyrimidine, and 17-chloro-16-dihydrotriazine steroids were synthesized by condensations of amidines with β-chlorovinyl aldehydes derived from natural hormones. The synthesized compounds were screened for cytotoxicity against breast cancer cells and showed IC50 values of 7.4 μM and higher. Compounds were tested against prostate cancer cells and exhibited antiproliferative activity with IC50 values of 9.4 μM and higher comparable to that of cisplatin. Lead compound 4a displayed selectivity in ERα-positive breast cancer cells. At 10 μM concentration, this heterosteroid inhibited 50% of the E2-mediated ERα activity and led to partial ERα down-regulation. The ERα reporter assay and immunoblotting were supported by the docking study, which showed the probable binding mode of compound 4a to the estrogen receptor pocket. Thus, heterosteroid 4a proved to be a selective ERα modulator with the highest antiproliferative activity against hormone-dependent breast cancer and can be considered as a candidate for further anticancer drug development. In total, the synthesized heterosteroids may be considered as new promising classes of active anticancer agents.

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“…It is a component of various biologically active compounds, which has led to the development of various anticancer agents. [ 7–19 ]…”

Section: Introductionmentioning

confidence: 99%

“…The literature data pertaining to epidermal growth factor receptor (EGFR) activation have been associated with the development and progression of human tumors, namely, breast, [ 7,14–16,50 ] lungs, [ 9,11,50,62 ] and prostate. [ 14 ] Furthermore, imidazopyridine and thiazolidinone derivatives have shown a potential anticancer activity against the most prevalent diagnosed cancers and the most common causes of cancer death, namely lung, breast, and prostate. Therefore, we chose three human cancer cell lines (MCF7 “breast,” A549 “human lung carcinoma,” and DU145 “prostate”) to assess the in vitro cytotoxicity potential of the synthesized compounds using the 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl tetrazolium bromide (MTT) assay.…”

Section: Introductionmentioning

confidence: 99%

Design, synthesis, and biological evaluation of imidazopyridine‐linked thiazolidinone as potential anticancer agents

Azhar

Husain

Alam

et al. 2020

Archiv der Pharmazie

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In this study, two series of imidazopyridine-linked thiazolidinone rings (5a-h and 6a-h) constituting 16 new compounds were synthesized and tested for their antiproliferative activity against a panel of three human cancer cell lines, that is, MCF-7 (human breast cancer), A549 (human lung cancer), and DU145 (human prostate cancer). Three compounds, 5h, 6f, and 6h, exhibited remarkable results against all three cell lines, but compound 6h was found to be the most active one against the breast cancer cell line. Among all the synthesized compounds, 6h displayed the highest antioxidant results. Furthermore, the potent compounds 5h, 6f, and 6h showed no signs of toxicity at doses ranging from 50 to 500 mg/kg of animal body weight. The biochemical parameters (SGOT and SGPT) of compound 6h nearly matched the control in hepatotoxicity studies. The molecular docking and MM-GBSADG binding studies are in agreement with the in vitro anticancer and antioxidant activity results. The most promising compound 6h was found to have the highest docking score and binding energy, and its absorption, distribution, metabolism, and excretion (ADME) parameters are in the acceptable range. Thus, it can be concluded that 6h, an imidazopyridine derivative endowed with a thiazolidinone ring system, has the potential to be developed as an anticancer agent.

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Synthesis and antiproliferative activity evaluation of steroidal imidazo[1,2-a]pyridines

Cited by 40 publications

References 42 publications

Investigation of the effect of steroidal imidazoheterocycles hormone derivatives on JEG-3 trophoblast cells of choriocarcinoma

Investigation of the effect of steroidal imidazoheterocycles hormone derivatives on JEG-3 trophoblast cells of choriocarcinoma

Steroidal Pyrimidines and Dihydrotriazines as Novel Classes of Anticancer Agents against Hormone-Dependent Breast Cancer Cells

Design, synthesis, and biological evaluation of imidazopyridine‐linked thiazolidinone as potential anticancer agents

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