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1.
Vanessa Brito Adriana Oliveira Santos Gilberto Alves Paulo Almeida Samuel Silvestre 《Molecules (Basel, Switzerland)》2022,27(18)
A series of novel 21E-arylidene-4-azapregn-5-ene steroids has been successfully designed, synthesized and structurally characterized, and their antiproliferative activity was evaluated in four different cell lines. Within this group, the 21E-(pyridin-3-yl)methylidene derivative exhibited significant cytotoxic activity in hormone-dependent cells LNCaP (IC50 = 10.20 µM) and T47-D cells (IC50 = 1.33 µM). In PC-3 androgen-independent cells, the steroid 21E-p-nitrophenylidene-4-azapregn-5-ene was the most potent of this series (IC50 = 3.29 µM). Considering these results, the 21E-(pyridin-3-yl)methylidene derivative was chosen for further biological studies on T47-D and LNCaP cells, and it was shown that this azasteroid seems to lead T47-D cells to apoptotic death. Finally, molecular docking studies were performed to explore the affinity of these 4-azapregnene derivatives to several steroid targets, namely 5α-reductase type 2, estrogen receptor α, androgen receptor and CYP17A1. In general, compounds presented higher affinity to 5α-reductase type 2 and estrogen receptor α. 相似文献
2.
Based on our previous researches, a novel phenylpyrimidine pharmacophore model was proposed and fifteen derivatives were synthesized and characterized by means of spectroscopy methods. The inhibitory effects of them were screened against HeLa cell line by virtue of MTT assay in vitro. The results indicate some of the phenylpyrimidine derivatives exhibit potent biological activities. Among them, compounds 6g and 6h exhibit the best activity at half maximal inhibitory concentrations of 1.5 and 2.8 μmol/L, respectively. These compounds also exhibit good activities against HepG2 cell line and MCF-7 cell line. FLT-3 kinase was screened as the most potent molecular target. Computational docking between compound 6g and FLT-3 was carried out to interpret the binding mode. The results show phenylpyrimidine derivatives have effective antitumor activities, which provides a base for further research of them as antitumor agents. 相似文献
3.
Ahmed A. Fadda Ehab Abdel‐Latif Ahmed Fekri Amal R. Mostafa 《Journal of heterocyclic chemistry》2019,56(3):804-814
Newly synthesized 1,2,3‐benzotriazine‐4‐one derivatives substituted at position‐3 were characterized by various analytical and spectral techniques. The in vitro antitumor activity was evaluated against three different cell lines (liver cells cancer, colorectal cancer, and breast cancer), where compounds 7b , 15 , and 25 showed strong antitumor activity with IC50 ranging from 5.54 to 16.26 μM. In addition, molecular modeling studies using MOE were performed to investigate their binding modes to the C‐Met kinase active site. Docking results demonstrated that all new compounds recognized the active sites of C‐Met kinase and form different types of bonding interactions with key active site amino acid residues. 相似文献
4.
Khalifa N. M. Alkahtani H. M. Al-Omar M. A. Bakheit A. H. 《Russian Journal of General Chemistry》2019,89(8):1683-1690
Russian Journal of General Chemistry - A new series of pyrido[2,3-d]pyrimidones incorporated pyrazoles and fused triazoles are synthesized and tested in vitro for cytotoxic effect against cancer... 相似文献
5.
《中国化学快报》1997,(3)
AsaresultOfthedevlOPmentOfetOPOSide(VPl6)andteaiPOSide(VM-26)asanticancertw,thesendSynheticanalOgUsOfthenaturailyoccuning~OtOkin(l)havebomuchrenewedinterestinrecentyears.Inourprevioushees",wefOundthatanumterOfhitroXy1opnltheledderivativesOf~yllOtoxinhadsignfficantanticancerAnvitywithInareddecreaseintoxidtycomParedwiththeParentcompoundlandVPl6.AseriesofSPinldeledderibovesOfthio-TEPA,'`,nitrosourea',andruboInyin8werealsoreportedtohavSUPeriorpharmaCOledtalpmprtiestotheirparentco… 相似文献
6.
依据生物电子等排原理,设计合成了13个全新结构的1,2-苯并噻嗪类化合物,其结构均经IR,1H NMR,13C NMR和MS确证.以A431,A549,MDA-MB-468和HL60 4种细胞株为活性筛选对象,采用四甲基偶氮唑盐(MTT)法进行初步的体外抗肿瘤活性研究.结果表明,部分化合物对肿瘤细胞有一定的抑制活性,其中化合物5b对A431具有显著的抑制活性,IC50值为1.57μmol/L,化合物9a对A431,A549和MDA-MB-468 3种细胞株的抑制活性均强于阳性对照药gefitinib.并采用Moe软件对所合成的化合物与表皮生长因子受体(EGFR)结合位点进行对接,以进一步阐释所合成化合物的作用靶标. 相似文献
7.
Chemistry of Natural Compounds - Ten 4β-N-substituted derivatives of 4′-O-demethylpodophyllotoxin were designed by aldehydes reacting with 4′-O-demethylpodophyllotoxin. Their... 相似文献
8.
Liu H.-Y. Wang T.-R. Sheng G.-H. Qin J. Sun J. 《Russian Journal of General Chemistry》2018,88(12):2601-2610
Russian Journal of General Chemistry - A series of novel 1,4-benzodioxan derivatives containing Schiff base are synthesized by the method of splicing active substructures. All compounds are assayed... 相似文献
9.
Continuing our ongoing studies on cytotoxic substances, we report the synthesis and cytotoxic properties of a series of symmetric 1,5‐diamino‐9,10‐anthraquinones with potentially bioreducible groups. Symmetric amination of 1,5‐dichloro‐9,10‐anthraquinone with the appropriate primary amines in the presence of DMF furnished the structurally related aminoanthraquinone analogs 1 – 19 . Their in vitro cytotoxic activity was evaluated using rat glioma C6 cells, human hepatoma G2 cells, and 2.2.15 cells. Several compounds exhibited very high antitumor activities in these assays. Compound 4 efficiently inhibited C6 cells, human hepatoma G2 cells, and 2.2.15 cells, as determined by means of the XTT colorimetric assay. The antiproliferative activity of 4 was markedly enhanced, reaching a potency comparable to those of the powerful anticancer agents mitoxantrone, adriamycin, and cisplatin. Biological evaluations and structure/activity relationships within this class of novel aminoanthraquinones are discussed. 相似文献
10.
Mykhaylo Frasinyuk Dimple Chhabria Victor Kartsev Haritha Dilip Samvel N. Sirakanyan Sivapriya Kirubakaran Anthi Petrou Athina Geronikaki Domenico Spinelli 《Molecules (Basel, Switzerland)》2022,27(14)
Despite extensive studies and the great variety of existing anticancer agents, cancer treatment remains an aggravating and challenging problem. Therefore, the development of novel anticancer drugs with a better therapeutic profile and fewer side effects to combat this persistent disease is still necessary. In this study, we report a novel series of benzothiazole and chromone derivatives that were synthesized and evaluated for their anticancer activity as an inhibitor of ATR kinase, a master regulator of the DDR pathway. The cell viability of a set of 25 compounds was performed using MTT assay in HCT116 and HeLa cell lines, involving 72 h incubation of the compounds at a final concentration of 10 µM. Cells incubated with compounds 2c, 7h and 7l were found to show viability ≤50%, and were taken forward for dose–response studies. Among the tested compounds, three of them (2c, 7h and 7l) showed higher potency, with compound 7l exhibiting the best IC50 values in both the cell lines. Compounds 2c and 7l were found to be equally cytotoxic towards both the cell lines, namely, HCT116 and HeLa, while compound 7h showed better cytotoxicity towards HeLa cell line. For these three compounds, an immunoblot assay was carried out in order to analyze the inhibition of phosphorylation of Chk1 at Ser 317 in HeLa and HCT116 cells. Compound 7h showed inhibition of pChk1 at Ser 317 in HeLa cells at a concentration of 3.995 µM. Further analysis for Chk1 and pChk1 expression was carried out in Hela cells by treatment against all the three compounds at a range of concentrations of 2, 5 and 10 µM, wherein compound 7h showed Chk1 inhibition at 2 and 5 µM, while pChk1 expression was observed for compound 7l at a concentration of 5 µM. To support the results, the binding interactions of the compounds with the ATR kinase domain was studied through molecular docking, wherein compounds 2c, 7h and 7l showed binding interactions similar to those of Torin2, a known mTOR/ATR inhibitor. Further studies on this set of molecules is in progress for their specificity towards the ATR pathway. 相似文献
11.
M. S. A. El-Gaby Z. H. Ismail S. M. Abdel-Gawad H. M. Aly M. M. Ghorab 《Phosphorus, sulfur, and silicon and the related elements》2013,188(10):2645-2654
The non-isolated adducts (3a,b) were used as key intermediates to synthesize some novel thiazolidine and thiophene derivatives. Compound (4) exhibited a remarkable antitumor activity against EAC cells compared with the Doxorubicin as a positive control. 相似文献
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13.
Ayen Ik Ulviye Acar evik Begüm Nurpelin Salk Yusuf
zkay 《Journal of heterocyclic chemistry》2019,56(1):142-152
The azole pharmacophore is still regarded as a viable lead structure for the synthesis of more effective antifungal agents. In this study, two novel series of imidazole derivatives containing dithiocarbamate (5a–5g) and (benz)azolethiol (6a–6n) side chains that are structurally related to the famous antifungal azole pharmacophore were synthesized, and the structures of them were characterized by spectral (IR, 1H NMR, 13C NMR, and MS spectra) analyses. The synthesized compounds were screened in vitro antifungal activity against pathogenic strains fungi. Theoretical ADME (absorption, distribution, metabolism, and excretion) predictions were calculated for final compounds. A molecular docking study of the most active compound with target “lanosterol 14α‐demethylase” (CYP51) was performed to unravel the mode of antifungal action. Compound 5e , which features imidazole and 4‐methoxybenzyl piperazine scaffolds, showed the most promising antifungal activity with an MIC50 value of 0.78 μg/mL against C. krusei. Effect of the compound 5e against ergosterol biosynthesis was observed by LC–MS–MS method, which is based on quantification of ergosterol level in C. krusei. 相似文献
14.
Gulipalli K. C. Ravula P. Bodige S. Endoori S. Cherukumalli P. K. R. Narendra Sharath Chandra J. N. Seelam N. 《Russian Journal of General Chemistry》2019,89(7):1502-1512
Russian Journal of General Chemistry - A novel series of thiophene-2-carboxamide derivatives are designed and synthesized, and their structures are confirmed by 1H and 13C NMR, and mass spectra.... 相似文献
15.
Katharigatta N. Venugopala Mohammed Habeebuddin Bandar E. Aldhubiab Afzal Haq Asif 《Molecules (Basel, Switzerland)》2021,26(17)
Indoles derived from both natural sources or artificial synthetic methods have been known to interact with aryl hydrocarbon receptors (AhR), and exhibit anticancer activity. In light of these attractive properties, a series of hybrid molecules with structural features of indoles, i.e., those bearing a pyrazoline nucleus, were evaluated for their enhanced anticancer activity. The designed molecules were subjected to molecular docking in order to screen for potential AhR interacting compounds, and the identified indolyl dihydropyrazole derivatives were synthesized. The synthesized compounds were characterized, and their cytotoxicity was evaluated against four human cancer cell lines using the MTT assay. Based on the Glide g-score, H-bonding interactions and bonding energy of 20 candidate molecules were selected for further analysis from the 64 initially designed molecules. These candidate molecules have shown promising anti-proliferative activity against the cell lines tested. Among these candidate molecules, the compounds with hydroxy phenyl substitution on the pyrazoline ring have shown potent activity across all the tested cell lines. The designed scaffold was proven effective for screening potential candidate molecules with anticancer properties, and may be further optimized structurally for yielding the ideal anti-tumorigenic compound for the treatment of various cancers. 相似文献
16.
Russian Journal of Organic Chemistry - New arylsulfanyl pyrazolylpyrazoline derivatives were synthesized via a facile protocol, and their structure was confirmed by FT-IR, 1H and 13C NMR, and mass... 相似文献
17.
Ramesh V. Rao G. Purna Chander Ramachandran D. Chakravarthy A. Kalyan 《Russian Journal of General Chemistry》2019,89(7):1491-1495
A series of new amide derivatives of imidazopyridine is synthesized and structures of the products are confirmed by 1H and 13C NMR, and mass spectral data. The synthesized derivatives are screened for their anticancer activity against four human cancer cell lines: lung cancer (A549), breast cancer (MCF-7), melanoma cancer (A375), and colon cancer (HT-29). Six synthesized compounds exhibit more potent activity than the control drug.
相似文献18.
Saeb Aliwaini Bassam Abu Thaher Ihab Al-Masri Nabil Shurrab Said El-Kurdi Dieter Schollmeyer Basem Qeshta Mariam Ghunaim Ren Csuk Stefan Laufer Lars Kaiser Hans-Peter Deigner 《Molecules (Basel, Switzerland)》2021,26(13)
Three novel pyrazolo-[4,3-e][1,2,4]triazolopyrimidine derivatives (1, 2, and 3) were designed, synthesized, and evaluated for their in vitro biological activity. All three compounds exhibited different levels of cytotoxicity against cervical and breast cancer cell lines. However, compound 1 showed the best antiproliferative activity against all tested tumor cell lines, including HCC1937 and HeLa cells, which express high levels of wild-type epidermal growth factor receptor (EGFR). Western blot analyses demonstrated that compound 1 inhibited the activation of EGFR, protein kinase B (Akt), and extracellular signal-regulated kinase (Erk)1/2 in breast and cervical cancer cells at concentrations of 7 and 11 µM, respectively. The results from docking experiments with EGFR suggested the binding of compound 1 at the ATP binding site of EGFR. Furthermore, the crystal structure of compound 3 (7-(4-bromophenyl)-9-(pyridin-4-yl)-7H-pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidine) was determined by single crystal X-ray analysis. Our work represents a promising starting point for the development of a new series of compounds targeting EGFR. 相似文献
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20.
Chandra Sekhar D. Venkata Rao D. V. Tejeswara Rao A. Lav Kumar U. Jha Anjali 《Russian Journal of General Chemistry》2019,89(4):770-779
Russian Journal of General Chemistry - A series of novel 5-phenyl-substituted 1,3,4-thiadiazole-2-amines were designed, synthesized, and screened for their antitumor and antitubercular activities.... 相似文献