scholarly journals A Novel and Different Approach for the Synthesis of Quinoline Derivatives Starting Directly from Nitroarenes and Their Evaluation as Anti-Cancer Agents

2020 ◽  
Vol 12 (1) ◽  
pp. 99
Author(s):  
Rizuana Sultana ◽  
Ravinder Reddy Tippanna
Keyword(s):  
Anticancer Activity ◽  
Cell Lines ◽  
Morphological Changes ◽  
Quinoline Derivatives ◽  
Mcf7 Cells ◽  
Independent Manner ◽  
Diverse Range ◽  
Chloride Dihydrate ◽  
Ic50 Values ◽  
Induced Apoptosis

A series of new quinoline derivatives (6-phenyl-6H-chromeno, [4,3-b] quinoline) have been prepared by using 4-chloro-2-phenyl-2H-chromene-3-carbaldehyde and various substituted nitroarenes as starting materials in the presence of Tin (II) chloride dihydrate and ethanol. The conversion in this synthesis involves the following steps (i) reduction of nitroarenes to anilines, (ii) Coupling of the anilines, chromene aldehydes (iii) Cyclization of resulting species and (iv) dehydration of cyclic intermediates. Several new quinolones have been prepared. We screened eight compounds of this novel series (6a-r) in three different cancer cell lines (B16F10, MCF7 and A549). The screened compounds showed moderate anticancer activity on two of the studied cell lines with best IC50 values of compound 6i (6.10±1.23 µM) and 6m (8.21±2.31 µM) on MCF7 cells. The selected compounds 6i and 6m led to morphological changes after treatment on MCF7 cell line. Interestingly, detailed studies suggested that the compounds 6i and 6m induced apoptosis in MCF7 cells in an oxidative stress independent manner without causing necrosis. In addition, we found destabilization of mitochondrial membrane potential behind the observed anticancer activity. Our results clearly indicate the promising anticancer potential of this novel series. This method is operationally simple and works with a diverse range of substrates.

scholarly journals Synthesis of Chromene 4 Aldehyde and 6-Phenyl-6h-Chromeno [4,3-B] Quinoline Derivatives as Anticancer and Apoptosis Inducing Agents

2021 ◽  
Vol 9 (10) ◽  
pp. 1764-1772
Author(s):  
Rizuana Sultana
Keyword(s):  
Cell Lines ◽  
Morphological Changes ◽  
Quinoline Derivatives ◽  
Significant Extent ◽  
Diverse Range ◽  
Synthetic Strategy ◽  
Induced Apoptosis ◽  
Apoptosis Inducing Agents ◽  
Mcf 7

Abstract: A series of novel chromene 3-aldehyde and quinoline derivatives have been synthesized using diversely substituted nitroarenes in the presence of In, dil. HCl, H2O (reductive amination) and evaluated for in vitro cytotoxic activity in three different cancer cell lines (MDA-MB-453, MCF-7, A549 and PC3). The synthetic strategy utilized to access these hybrids is operationally simple and works with great substrate scope. Interestingly, compound 6i was induced apoptosis to a significant extent in MDA-MB-453 cell lines. And these selected compounds 6i was led to morphological changes after treatment with MDA-MB-453 cell lines and found clear destabilization of mitochondrial membrane potential behind the observed anticancer activity. This strategy is operationally simple and works with a diverse range of substrates and warrants future investigations for further anticancer drug development.

scholarly journals Catalyst-Free Synthesis of Novel 6-Phenyl-6H-chromeno [4, 3-b] quinoline Derivatives at RT: Their Further Structure Evaluation Leads to Potential Anti-cancer Agents

2017 ◽  
Vol 12 (7) ◽  
pp. 1934578X1701200 ◽  
Author(s):  
Alleni Suman Kumar ◽  
Rathod Aravind Kumar ◽  
Vavilapally Satyanarayana ◽  
Elala Pravardhan Reddy ◽  
Boggu Jagan Mohan Reddy ◽  
...  
Keyword(s):  
Cell Lines ◽  
Preliminary Data ◽  
Model Compound ◽  
Structure Evolution ◽  
Quinoline Derivatives ◽  
Diverse Range ◽  
Anti Cancer ◽  
Ic50 Values ◽  
Novel Method ◽  
Structure Evaluation

A variety of novel quinoline derivatives (6-phenyl-6 H-chromeno [4,3- b] quinoline) have been prepared by using 4-chloro-2-phenyl-2 H-chromene-3-carbaldehyde and various substituted of aromatic anilines as starting materials. This is the first example on the preparation of quinolines through this novel method. And the resulting quinoline derivatives further structure evolution is leads to an anti cancer agents. Our preliminary data of model compound (7i) on three cancer cell lines (B16F10, MCF7 and A549) suggested decent anticancer activity on two cell lines (B16F10 and MCF7) with IC50 values of 14.8 and 21.32 μM, respectively. This method is operationally simple and works with a diverse range of substrates.

Isolation of New Glycosides from Anemarrhena Asphodeloides Rhizome and Screening of their Anticancer Activity

2019 ◽  
Vol 16 (6) ◽  
pp. 474-477 ◽  
Author(s):  
Pham Van Khang ◽  
Nguyen Thi Hien Lan ◽  
Le Quang Truong ◽  
Mai Thi Minh Chau ◽  
Mai Xuan Truong ◽  
...  
Keyword(s):  
Anticancer Activity ◽  
Spectral Data ◽  
Cell Lines ◽  
Cancer Cell ◽  
Spectroscopic Analysis ◽  
2D Nmr ◽  
Ic50 Values ◽  
Nmr Techniques ◽  
Inhibitory Activities ◽  
Anemarrhena Asphodeloides

In this report, two new steroidal glycosides were isolated and determined from n-butanol fraction of A.asphodeloides. The structures were confirmed in comparison with the spectral data of known compounds by using different spectroscopic analysis approaches including 1D & 2D-NMR techniques and HRMS. The anti-proliferation screening against cancer cell lines A549 and HeLa indicated that compound 1 exhibited good inhibitory activities with IC50 values of 0.79 and 0.55 µg/mL, respectively.

Naphthoquinone-based hydrazone hybrids: synthesis and potent activity against cancer cell lines

2020 ◽  
Vol 16 ◽  
Author(s):  
Délis Galvão Guimarães ◽  
Arlan de Assis Gonsalves ◽  
Larissa Araújo Rolim ◽  
Edigênia Cavalcante Araújo ◽  
Victória Laysna dos Anjos Santos ◽  
...  
Keyword(s):  
Anticancer Activity ◽  
Cell Lines ◽  
Cancer Cell ◽  
Biological Activities ◽  
Supporting Electrolyte ◽  
Cancer Cell Lines ◽  
Molecular Structures ◽  
Cytotoxic Activities ◽  
Electrochemical Studies ◽  
Ic50 Values

Background: Natural naphthoquinones have shown diversified biological activities including antibacterial, antifungal, antimalarial, and cytotoxic activities. However, they are also compounds with acute cytotoxicity, immunotoxicity, carcinogenesis, and cardio- and hepatotoxicity, then the modification at their redox center is an interesting strategy to overcome such harmful activity. Objective: In this study, four novel semisynthetic hydrazones, derived from the isomers α- and β-lapachones (α and β, respectively) and coupled with the drugs hydralazine (HDZ) and isoniazid (ACIL), were prepared, evaluated by electrochemical methods and assayed for anticancer activity. Method: The semisynthetic hydrazones were obtained and had their molecular structures established by NMR, IR, and MS. Anticancer activity was evaluated by cell viability determined by reduction of 3-(4,5-dimethyl-2-thiazol)-2,5-diphenyl-2H-tetrazolium bromide (MTT). The electrochemical studies, mainly cyclic voltammetry, were performed, in aprotic and protic media. Result: The study showed that the compounds 2, 3, and 4 were active against at least one of the cancer cell lines evaluated, being compounds 3 and 4 the most cytotoxic. Toward HL-60 cells, compound 3 was 20x more active than β-lapachone, and 3x more cytotoxic than doxorubicin. Furthermore, 3 showed an SI value of 39.62 for HL-60 cells. Compound 4 was active against all cancer cells tested, with IC50 values in the range 2.90–12.40 μM. Electrochemical studies revealed a profile typical of self-protonation and reductive cleavage, dependent on the supporting electrolyte. Conclusion: These results therefore indicate that compounds 3 and 4 are strong candidates as prototypes of new antineoplastic drugs.

scholarly journals Antiproliferative Efficacy of N-(3-chloro-4-fluorophenyl)-6,7-dimethoxyquinazolin-4-amine, DW-8, in Colon Cancer Cells Is Mediated by Intrinsic Apoptosis

Molecules ◽  
2021 ◽  
Vol 26 (15) ◽  
pp. 4417
Author(s):  
Rabin Neupane ◽  
Saloni Malla ◽  
Mariam Sami Abou-Dahech ◽  
Swapnaa Balaji ◽  
Shikha Kumari ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Colon Cancer Cells ◽  
Apoptotic Pathway ◽  
Anticancer Efficacy ◽  
Colon Cell ◽  
Ic50 Values ◽  
Induced Apoptosis

A novel series of 4-anilinoquinazoline analogues, DW (1–10), were evaluated for anticancer efficacy in human breast cancer (BT-20) and human colorectal cancer (CRC) cell lines (HCT116, HT29, and SW620). The compound, DW-8, had the highest anticancer efficacy and selectivity in the colorectal cancer cell lines, HCT116, HT29, and SW620, with IC50 values of 8.50 ± 2.53 µM, 5.80 ± 0.92 µM, and 6.15 ± 0.37 µM, respectively, compared to the non-cancerous colon cell line, CRL1459, with an IC50 of 14.05 ± 0.37 µM. The selectivity index of DW-8 was >2-fold in colon cancer cells incubated with vehicle. We further determined the mechanisms of cell death induced by DW-8 in SW620 CRC cancer cells. DW-8 (10 and 30 µM) induced apoptosis by (1) producing cell cycle arrest at the G2 phase; (2) activating the intrinsic apoptotic pathway, as indicated by the activation of caspase-9 and the executioner caspases-3 and 7; (3) nuclear fragmentation and (4) increasing the levels of reactive oxygen species (ROS). Overall, our results suggest that DW-8 may represent a suitable lead for developing novel compounds to treat CRC.

scholarly journals Synthesis of Novel 2-Thioxothiazolidin-4-one and Thiazolidine-2, 4-dione Derivatives as Potential Anticancer Agents

2018 ◽  
Vol 13 (5) ◽  
pp. 1934578X1801300
Author(s):  
Alleni Suman Kumar ◽  
Rathod Aravind Kumar ◽  
Elala Pravardhan Reddy ◽  
Vavilapalli Satyanarayana ◽  
Jajula Kashanna ◽  
...  
Keyword(s):  
Anticancer Activity ◽  
Cell Lines ◽  
Cancer Cell ◽  
Anticancer Agents ◽  
Preliminary Data ◽  
Cancer Cell Lines ◽  
Structure Evolution ◽  
Model Compounds ◽  
Diverse Range ◽  
Novel Method

A variety of novel thiazolidine derivatives (2-thioxothiazolidin-4-one and thiazolidine-2, 4-dione derivatives) have been prepared by using 2,4-diphenyl-2 H-chromene-3-carbaldehyde and its derivatives as starting materials. This is the first example of the preparation of thiazolidine derivatives through this novel method. Structure evolution of the resulting thiazolidine derivatives leads to anticancer agents. Our preliminary data for some model compounds on three cancer cell lines (MCF7, A549 and B-16) suggested reasonable anticancer activity against the A549 and B-16 cell lines, with IC50 values of 20.7 and 20.4 μM, respectively. This method is operationally simple and works with a diverse range of substrates.

scholarly journals The Cardiac Glycoside Deslanoside Exerts Anticancer Activity in Prostate Cancer Cells by Modulating Multiple Signaling Pathways

Cancers ◽  
2021 ◽  
Vol 13 (22) ◽  
pp. 5809
Author(s):  
Mingcheng Liu ◽  
Qingqing Huang ◽  
Jun A ◽  
Linyue Li ◽  
Xiawei Li ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Cycle ◽  
Anticancer Activity ◽  
Signaling Pathways ◽  
Cell Lines ◽  
Cardiac Glycoside ◽  
Cardiac Glycosides ◽  
Disease Free Survival ◽  
Diverse Range ◽  
Multiple Signaling

Prostate cancer (PCa) is a leading cause of cancer-related deaths among men worldwide, and novel therapies for advanced PCa are urgently needed. Cardiac glycosides represent an attractive group of candidates for anticancer repurposing, but the cardiac glycoside deslanoside has not been tested for potential anticancer activity so far. We found that deslanoside effectively inhibited colony formation in vitro and tumor growth in nude mice of PCa cell lines 22Rv1, PC-3, and DU 145. Such an anticancer activity was mediated by both the cell cycle arrest at G2/M and the induction of apoptosis, as demonstrated by different functional assays and the expression status of regulatory proteins of cell cycle and apoptosis in cultured cells. Moreover, deslanoside suppressed the invasion and migration of PCa cell lines. Genome-wide expression profiling and bioinformatic analyses revealed that 130 genes were either upregulated or downregulated by deslanoside in both 22Rv1 and PC-3 cell lines. These genes enriched multiple cellular processes, such as response to steroid hormones, regulation of lipid metabolism, epithelial cell proliferation and its regulation, and negative regulation of cell migration. They also enriched multiple signaling pathways, such as necroptosis, MAPK, NOD-like receptor, and focal adhesion. Survival analyses of the 130 genes in the TCGA PCa database revealed that 10 of the deslanoside-downregulated genes (ITG2B, CNIH2, FBF1, PABPC1L, MMP11, DUSP9, TMEM121, SOX18, CMPK2, and MAMDC4) inversely correlated, while one deslanoside-upregulated gene (RASD1) positively correlated, with disease-free survival in PCa patients. In addition, one deslanoside-downregulated gene (ENG) inversely correlated, while three upregulated genes (JUN, MXD1, and AQP3) positively correlated with overall survival in PCa patients. Some of the 15 genes have not been implicated in cancer before. These findings provide another candidate for repurposing cardiac glycosides for anticancer drugs. They also suggest that a diverse range of molecular events underlie deslanoside’s anticancer activity in PCa cells.

Molecular Docking and In Vitro Anticancer Screening of Synthesized Arylthiazole linked 2H-indol-2-one Derivatives as VEGFR-2 Kinase Inhibitors

2021 ◽  
Vol 21 ◽  
Author(s):  
Nishtha Shalmali ◽  
Sandhya Bawa ◽  
Md Rahmat Ali ◽  
Sourav Kalra ◽  
Raj Kumar ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Anticancer Activity ◽  
Cell Lines ◽  
Cancer Cell ◽  
Active Sites ◽  
Colorectal Adenocarcinoma ◽  
Kinase Inhibitors ◽  
Adenocarcinoma Cells ◽  
Ic50 Values

Background: Indoline-2,3-dione comprises a leading course group of heterocycles endowed with appealing biological actions, including anticancer activity. There are significant justifications for exploring the anticancer activity of Schiff base derivatives of isatin as a vast number of reports have documented remarkable antiproliferative action of isatin nucleus against various cancer cell lines. Aims and Objectives: A series of arylthiazole linked 2H-indol-2-one derivatives (5a-t) was designed and synthesized as potential VEGFR-2 kinase inhibitors keeping the essential pharmacophoric features of standard drugs, like sunitinib, sorafenib, nintedanib, etc. They were evaluated for their in vitro anticancer activity. The aim of this study was to investigate and assess the anticancer potential of isatin-containing compounds along with their kinase inhibition activity. Methods: The title compounds were synthesized by reacting substituted isatins with para-substituted arylthiazoles using appropriate reaction conditions. Selected synthesized derivatives went under preliminary screening against a panel of 60 cancer cell lines at NCI, the USA, for single-dose and five dose assays. Molecular docking was performed to explore the binding and interactions with the active sites of the VEGFR-2 receptor (PDB Id: 3VHE). Derivatives 5a, 5b, 5c, 5d, 5g, 5h, and 5m were assessed for in vitro inhibition potency against Human VEGFR-2 using ELISA (Enzyme-Linked Immunosorbent Assay) kit. All the target compounds were determined against human colon cancer cell line SW480 (colorectal adenocarcinoma cells). Cellular apoptosis/necrosis was determined by flow cytometry using annexin V-FITC. DNA content of the cells was analyzed by flow cytometry and the cycle distribution was quantified. Results: Compounds 5a and 5g exhibited noteworthy inhibition during a five-dose assay against a panel of 60 cell lines with MID GI50 values of 1.69 and 1.54 µM, respectively. Also, both the lead compounds 5a and 5g demonstrated promising VEGFR-2 inhibitory activity with IC50 values of 5.43±0.95 and 9.63±1.32 µM, respectively. The aforesaid potent compounds were found effective against SW480 (colorectal adenocarcinoma cells) with IC50 values of 31.44 µM and 106.91 µM, respectively. Compound 5a was found to arrest the cell cycle at the G2/M phase, increasing apoptotic cell death. The docking study also supported VEGFR-2 inhibitory activity as both compounds 5a and 5g displayed promising binding and interactions with the active sites of VEGFR-2 receptor (PDB: 3VHE) with docking scores -9.355 and -7.758, respectively. All the compounds obeyed Lipinski’s rule of five. Conclusion: Indoline-2,3-dione and thiazole have huge potential to be considered a steer combination approach for developing promising kinase inhibitors as cancer therapeutics.

Arsenic Trioxide and Melarsoprol Induce Programmed Cell Death in Myeloid Leukemia Cell Lines and Function in a PML and PML-RAR Independent Manner

Blood ◽  
1998 ◽  
Vol 92 (5) ◽  
pp. 1497-1504 ◽  
Author(s):  
Zhu-Gang Wang ◽  
Roberta Rivi ◽  
Laurent Delva ◽  
Andrea König ◽  
David A. Scheinberg ◽  
...  
Keyword(s):  
Cell Line ◽  
Arsenic Trioxide ◽  
Cell Lines ◽  
Myeloid Leukemia ◽  
Leukemia Cell ◽  
Nuclear Bodies ◽  
Independent Manner ◽  
Leukemia Cell Lines ◽  
Induced Apoptosis ◽  
Myeloid Leukemia Cell

Abstract Inorganic arsenic trioxide (As2O3) and the organic arsenical, melarsoprol, were recently shown to inhibit growth and induce apoptosis in NB4 acute promyelocytic leukemia (APL) and chronic B-cell leukemia cell lines, respectively. As2O3 has been proposed to principally target PML and PML-RAR proteins in APL cells. We investigated the activity of As2O3 and melarsoprol in a broader context encompassing various myeloid leukemia cell lines, including the APL cell line NB4-306 (a retinoic acid–resistant cell line derived from NB4 that no longer expresses the intact PML-RAR fusion protein), HL60, KG-1, and the myelomonocytic cell line U937. To examine the role of PML in mediating arsenical activity, we also tested these agents using murine embryonic fibroblasts (MEFs) and bone marrow (BM) progenitors in which the PML gene had been inactivated by homologous recombination. Unexpectedly, we found that both compounds inhibited cell growth, induced apoptosis, and downregulated bcl-2 protein in all cell lines tested. Melarsoprol was more potent than As2O3 at equimolar concentrations ranging from 10−7 to 10−5 mol/L. As2O3 relocalized PML and PML-RAR onto nuclear bodies, which was followed by PML degradation in NB4 as well as in HL60 and U937 cell lines. Although melarsoprol was more potent in inhibiting growth and inducing apoptosis, it did not affect PML and/or PML-RAR nuclear localization. Moreover, both As2O3 and melarsoprol comparably inhibited growth and induced apoptosis of PML+/+ and PML−/− MEFs, and inhibited colony-forming unit erythroid (CFU-E) and CFU granulocyte-monocyte formation in BM cultures of PML+/+ and PML−/− progenitors. Together, these results show that As2O3 and melarsoprol inhibit growth and induce apoptosis independent of both PML and PML-RAR expression in a variety of myeloid leukemia cell lines, and suggest that these agents may be more broadly used for treatment of leukemias other than APL. © 1998 by The American Society of Hematology.

scholarly journals Design, Synthesis, and Structural Characterization of Novel Diazaphenothiazines with 1,2,3-Triazole Substituents as Promising Antiproliferative Agents

Molecules ◽  
2019 ◽  
Vol 24 (23) ◽  
pp. 4388 ◽  
Author(s):  
Morak-Młodawska ◽  
Pluta ◽  
Latocha ◽  
Jeleń ◽  
Kuśmierz
Keyword(s):  
Anticancer Activity ◽  
Cell Lines ◽  
Human Fibroblasts ◽  
Human Tumor ◽  
Design Synthesis ◽  
Human Tumor Cell Lines ◽  
Ic50 Values ◽  
Normal Human ◽  
Low Cytotoxicity

A series of novel 1,2,3-triazole-diazphenothiazine hybrids was designed, synthesized, and evaluated for anticancer activity against four selected human tumor cell lines (SNB-19, Caco-2, A549, and MDA-MB231). The majority of the synthesized compounds exhibited significant potent activity against the investigated cell lines. Among them, compounds 1d and 4c showed excellent broad spectrum anticancer activity, with IC50 values ranging from 0.25 to 4.66 μM and 0.25 to 6.25 μM, respectively. The most promising compound 1d, possessing low cytotoxicity against normal human fibroblasts NHFF, was used for gene expression analysis using reverse transcription–quantitative real-time PCR (RT–qPCR). The expression of H3, TP53, CDKN1A, BCL-2, and BAX genes revealed that these compounds inhibited the proliferation in all cells (H3) and activated mitochondrial events of apoptosis (BAX/BCL-2).

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