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 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 novel thiourea-/urea-benzimidazole derivatives as anticancer agents

2021 ◽  
Vol 19 (1) ◽  
pp. 1062-1073
Author(s):  
Lamia A. Siddig ◽  
Mohammad A. Khasawneh ◽  
Abdelouahid Samadi ◽  
Haythem Saadeh ◽  
Nael Abutaha ◽  
...  
Keyword(s):  
Cell Lines ◽  
Anticancer Agents ◽  
Caspase 3 ◽  
Benzimidazole Derivatives ◽  
Spectroscopic Techniques ◽  
Thiourea Derivatives ◽  
Ethidium Bromide Staining ◽  
Induced Apoptosis ◽  
Mcf 7

Abstract A new series of urea and thiourea derivatives containing benzimidazole group as potential anticancer agents have been designed and synthesized. The structures of the synthesized compounds were characterized and confirmed by spectroscopic techniques such as 1H NMR, 13C NMR, and mass spectrometry. In vitro anticancer assay against two breast cancer (BC) cell lines, MDA-MB-231ER(−)/PR(−) and MCF-7ER(+)/PR(+), revealed that the cytotoxicity of 1-(2-(1H-benzo[d]imidazol-2-ylamino)ethyl)-3-p-tolylthiourea (7b) and 4-(1H-benzo[d]imidazol-2-yl)-N-(3-chlorophenyl)piperazine-1-carboxamide (5d) were higher in MCF-7 with IC50 values of 25.8 and 48.3 µM, respectively, as compared with MDA-MB-231 cells. Furthermore, 7b and 5d were assessed for their apoptotic potential using 4′,6-diamidino-2-phenylindole, acridine orange/ethidium bromide staining, and Caspase-3/7. After incubation with MCF-7, the compounds 7b and 5d induced apoptosis through caspase-3/7 activation. In conclusion, the compounds 7b and 5d are potential candidates for inducing apoptosis in different genotypic BC cell lines.

In Vitro Anticancer Evaluation of Some Synthesized 2H-Quinolinone and Halogenated 2H-Quinolinone Derivatives as Therapeutic Agents

2020 ◽  
Vol 20 (18) ◽  
pp. 2304-2315
Author(s):  
Rahma M. Abd El-Aziz ◽  
Islam Zaki ◽  
Ibrahim M. El-Deen ◽  
Marwa S. Abd-Rahman ◽  
Faten Z. Mohammed
Keyword(s):  
Cell Lines ◽  
Cancer Cell ◽  
Anticancer Agents ◽  
Cancer Cell Lines ◽  
Normal Breast ◽  
Cytotoxic Agents ◽  
Dna Flow Cytometry ◽  
Induced Apoptosis ◽  
Mcf 7

Background: Searching for new cytotoxic agents with apoptosis induction may represent a viable strategy for cancer treatment to overcome the increased resistance to available anticancer agents. Objective: The purpose of the current study was aimed at preparation and anticancer evaluation of two new series of 2H-quinolinone and halogenated 2H-quinolinone derivatives against two cancer cell lines. Methods: Two new series of 2H-quinolinone and halogenated 2H-quinolinone derivatives were prepared and screened for their cytotoxicity against breast MCF-7 and liver HepG-2 cancer cell lines as well as normal breast MCF-10a. Results: The tested molecules revealed good cytotoxicity and selectivity toward cancer cell lines relative to normal cells. These compounds were analyzed by DNA flow cytometry on MCF-7 cells. They were found to cause G2/M phase arrest and induced apoptosis at the pre-G1 phase. In addition, increased caspase 3/7 activity and decreased osteopontin expression verified the apoptotic activity. Conclusion: The potent compounds discovered in this study can be a hit for the discovery of new cytotoxic agents and are worthy of further investigation.

scholarly journals IN VITRO EVALUATION OF ANTICANCER POTENTIAL OF ERYTHRINA VARIEGATA L. ON BREAST CANCER CELL LINES

2017 ◽  
Vol 10 (7) ◽  
pp. 305
Author(s):  
Vaishali Rai M ◽  
Vinitha Ramanath Pai ◽  
Samuel Kevin ◽  
Herga P Kedilaya
Keyword(s):  
Cell Lines ◽  
Anticancer Agents ◽  
Morphological Changes ◽  
Treated Group ◽  
Breast Cancer Cell Lines ◽  
Liquid Chromatography Mass Spectrometry ◽  
Erythrina Variegata ◽  
Ic50 Value ◽  
Mcf 7

Objective: Species of Erythrina variegata L. is reported to be used in the treatment of cancer in traditional/folklore medicine which could be explored for their anticancer potential. We aimed to evaluate the anticancer activity of crude extracts of the leaves of E. variegata with two solvents; explore the mechanism of cytotoxicity with the effective extract and correlation with the phytochemicals in the extract.Methods: The extracts with Erythrina variegata L methanol (EVM) and chloroform (EVC) as solvents were screened for cytotoxicity by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium assay on MDA-MB-231 and MCF-7 cell lines. The effective extract was further evaluated on MDA-MB-231 cells by nucleoprotein content estimation, and cell morphology was studied. High resolution liquid chromatography mass spectrometry (HRLCMS) of EVM was done to find the phytochemical composition.Results: Among the two extracts, EVM was effective at an inhibitory concentration (IC50) value of 92 μg/ml and 143 μg/ml on MCF-7 and MDA-MB-231 cells, respectively. At the IC50 value (143 μg/ml) the nucleoprotein content of the cells was 58.2%, and the apoptotic index was calculated to be 51.8%. EVM treated group showed significant morphological changes suggestive of apoptosis. HRLCMS revealed the presence of rutin, podocarpatriene, and cepharanthine which are known to be cytotoxic.Conclusion: This report is a contribution toward the validation of E. variegata as a potential source of anticancer agents.

scholarly journals Investigating the in Vitro Antiproliferative and Apoptosis-Inducing Effects of Pyranochromene Derivatives

2020 ◽  
Vol 11 (3) ◽  
pp. 10987-10995
Keyword(s):  
Cell Lines ◽  
Biological Activities ◽  
Para Position ◽  
Lead Compounds ◽  
Three Component Reaction ◽  
Anti Cancer ◽  
Important Health ◽  
Induced Apoptosis ◽  
Mcf 7

Cancer is one of the important health problems, and researchers continue their efforts to discover new anti-cancer agents. Coumarins (chromene-2-ones), a group of natural metabolites, have shown different biological activities based on their substitutions. In this study, 15 compounds of 1,5-dihydropyrano[2,3-c]chromene were synthesized by three-component reaction and investigated for the antiproliferative activity on the breast (MCF-7), colorectal (SW48 and HT-29), lung (A549), and brain (U-87 MG) cancer cell lines as well as two normal cell lines (3T3 and HUVEC). The apoptosis/necrosis-inducing effect of the selected compounds was determined on the MCF-7 cell line by flow cytometry. The results showed that the compounds bearing a moiety on their phenyl ring's para position had potent cytotoxic effects on the tested cell lines. These compounds induced apoptosis in MCF-7 cells. The compounds were also toxic for 3T3 and HUVECs and did not display a high selectivity for tumor cells. Our results revealed that the compounds having a moiety at the para position of their phenyl ring might be suitable lead compounds for the synthesis of potent anti-cancer agents.

(Substituted)-benzo[b]thiophene-4-carboxamide Synthesis and Antiproliferative Activity Study

2020 ◽  
Vol 17 (5) ◽  
pp. 563-573 ◽  
Author(s):  
Chandrakant Dhondiram Pawar ◽  
Dattatraya Navnath Pansare ◽  
Devanand Baburao Shinde
Keyword(s):  
Anticancer Activity ◽  
Cell Lines ◽  
Proliferative Activity ◽  
Thiophene Ring ◽  
Amide Group ◽  
Peptide Coupling ◽  
Ic50 Value ◽  
Important Building Block ◽  
Mcf 7

Background: Thiophene ring forms important building block in medicinal chemistry. Literature reveals that thiophene ring in combination with different groups shows different activity. By keeping these things in mind we have designed and synthesized a new series of amide and sulfonamide coupled thiophene. A series of novel substituted 3-sulfamoylbenzo[b]thiophene-4- carboxamide molecules containing sulfonamide and amide group were designed, synthesized and used for anti-proliferative activity study. Methods: The final compounds 16-36 were synthesized by using series of reactions comprising sulfonation, sulfonamide coupling, hydrolysis and peptide coupling. The yields of compounds 16- 36 are in the range of 90-98%. The structures of the synthesized compounds were elucidated and confirmed by 1H NMR, 13C NMR, LCMS and the purity was checked through HPLC analysis. The compounds were further tested for their in vitro anticancer activity against a series of cell lines A549, HeLa, MCF-7 and Du-145. Results: The intermediates 8-13, 15 and final compounds 16-36 were synthesized in good yields. The synthesized compounds were further tested for their anticancer activity and most of compounds showed moderate to good anticancer activity against all four cell lines. Conclusion: We have synthesized 21 compounds and were screened for anticancer activity against MCF-7, HeLa, A-549 and Du-145 cancer cell lines. Most of the compounds were active for tested cell lines with IC50 value in the range of 1.81 to 9.73 μM. The compounds 18, 19, 21, 25, 30, 31 and 33 are most active in cell line data with IC50 value in the range of 1.81 to 2.52 μM.

In Vitro Antitumor Evaluation of Some Hybrid Molecules Containing Coumarin and Quinolinone Moieties

2020 ◽  
Vol 19 (16) ◽  
pp. 2010-2018
Author(s):  
Youstina W. Rizzk ◽  
Ibrahim M. El-Deen ◽  
Faten Z. Mohammed ◽  
Moustafa S. Abdelhamid ◽  
Amgad I.M. Khedr
Keyword(s):  
Cell Cycle ◽  
Cell Lines ◽  
Cancer Cell ◽  
Anticancer Agents ◽  
Topoisomerase Ii ◽  
Cancer Cell Lines ◽  
Bax Protein ◽  
Hybrid Molecules ◽  
Mcf 7

Background: Hybrid molecules furnished by merging two or more pharmacophores is an emerging concept in the field of medicinal chemistry and drug discovery. Currently, coumarin hybrids have attracted the keen attention of researchers to discover their therapeutic capability against cancer. Objective: The present study aimed to evaluate the in vitro antitumor activity of a new series of hybrid molecules containing coumarin and quinolinone moieties 4 and 5 against four cancer cell lines. Materials and Methods: A new series of hybrid molecules containing coumarin and quinolinone moieties, 4a-c and 5a-c, were synthesized and screened for their cytotoxicity against prostate PC-3, breast MCF-7, colon HCT- 116 and liver HepG2 cancer cell lines as well as normal breast Hs-371 T. Results: All the synthesized compounds were assessed for their in vitro antiproliferative activity against four cancer cell lines and several compounds were found to be active. Further in vitro cell cycle study of compounds 4a and 5a revealed MCF-7 cells arrest at G2 /M phase of the cell cycle profile and induction apoptosis at pre-G1 phase. The apoptosis-inducing activity was evidenced by up-regulation of Bax protein together with the downregulation of the expression of Bcl-2 protein. The mechanism of cytotoxic activity of compounds 4a and 5a correlated to its topoisomerase II inhibitory activity. Conclusion: Hybrid molecules containing coumarin and quinolinone moieties represents a scaffold for further optimization to obtain promising anticancer agents.

New Ferrocene Compounds as Selective Cyclooxygenase (COX-2) Inhibitors: Design, Synthesis, Cytotoxicity and Enzyme-inhibitory Activity

2018 ◽  
Vol 18 (2) ◽  
pp. 295-301 ◽  
Author(s):  
Shabnam Farzaneh ◽  
Elnaz Zeinalzadeh ◽  
Bahram Daraei ◽  
Soraya Shahhosseini ◽  
Afshin Zarghi
Keyword(s):  
Cell Lines ◽  
Inhibitory Activity ◽  
Fibroblast Cell ◽  
Breast Cancer Cell Lines ◽  
Ferrocene Derivatives ◽  
Cox 2 ◽  
Cytotoxicity Effects ◽  
Cox 2 Inhibitors ◽  
Mcf 7

Background: Due to the astonishing properties of ferrocene and its derivatives, it has a broad application in diverse areas. Numerous ferrocene derivatives demonstrated anti-proliferative activity. Also COX-2, as a key isoenzyme for production of prostaglandins, is frequently overexpressed in various cancers. It is now recognized that COX-2 over expression promotes tumorigenic functions which can be suppressed by COX-2 inhibitors, a phenomenon useful for the preventing of tumor progression. The combination of COX-2 inhibitors with other anti-cancer or cancer prevention drugs may reduce their side effects in future cancer prevention and treatment. Objective: Owing to high anticancer potential of ferrocene derivatives and considerable COX-2 inhibitory and cytotoxicity effects of our previously synthesized chalcones, we decided to incorporate the ferrocenyl moiety into appropriate COX-2 inhibitor chalcone based scaffold, to evaluate COX-2 inhibitory activity as well as anticancer activities. Methods: Chalcones were synthesized via clasien-schmidt condensation of methylsulfonyl aldehyde and acetyl ferrocene. Further different amines with solvent free and ultra sound condition were reacted with chalcones to have different 1-ferrocenyl-3-amino carbonyl compounds. Docking study was carried out with Auto Dock vina software. All the newly-synthesized compounds were evaluated for their cyclooxygenase-2 (COX-2) inhibitory activity using chemiluminescent enzyme assays as well as cytotoxicity activity against MCF-7 and T47D and fibroblast cell lines by MTT assay. Results: In vitro COX-1/COX-2 inhibition studies demonstrated that all compounds were selective inhibitors of the COX-2 isozyme with IC50 values in the highly potent 0.05-0.12 µM range, and COX-2 selectivity indexes (SI) in the 148.3-313.7 range. These results indicated that either potency or selectivity of COX-2 inhibitory activity was affected by the nature and size of the substituents on C-3 of propane-1-one. Also anti-proliferative and toxicity activities of synthesized compounds against breast cancer cell lines MCF-7 and T47D and fibroblast cell lines showed that the synthesized compounds had mild to moderate cytotoxicity against MCT7 and T47D breast cancer cell lines at 10 µM concentration. In vitro COX-1/COX-2 inhibition studies and anticancer activity against MCF-7, identified 1-ferrocenyl-3-(4-methylsulfonylphenyl) propen-1-one as a potent compound (IC50 COX-2 = 0.05 µM, MCF-7: % inhibition (at concentration of 10 µM) = 32.7%), and also 1-ferrocenyl-3- (propan-1-amine)-3-(4-methylsulfonylphenyl) propan-1-one showed the most selectivity on COX-2 inhibition (selectivity index= 313.7). Conclusion: A novel group of ferrocene compounds, possessing a methyl sulfonyl COX-2 pharmacophore were synthesized to investigate the effect of different substituents on selectivity and potency of COX-2 inhibitory activity and their cytotoxicity effects. This study indicates that 1-ferrocenyl-3-amino carbonyl compounds having ferrocene motif and methyl sulfonyl COX-2 pharmacophore is a suitable scaffold to design COX-2 inhibitors and anti-cancer agents.

In Vitro Evaluation of Chitosan Induced Cytotoxicity against Cancerous Cell lines: MCF-7, Saos-2 and HeLa

2019 ◽  
Vol 19 ◽  
Author(s):  
Zeinab Abedian ◽  
Niloofar Jenabian ◽  
Ali Akbar Moghadamnia ◽  
Ebrahim Zabihi ◽  
Roghayeh Pourbagher ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Cell Lines ◽  
Anticancer Agents ◽  
Fibroblast Cells ◽  
Apoptosis Induction ◽  
Cytotoxic Effects ◽  
Cancerous Cell ◽  
Significant Concentration ◽  
Mcf 7

Objective/ Background: Cancer is still the most common cause of morbidity in world and new powerful anticancer agents without severe side effects from natural sources is important. Methods: The evaluation of cytotoxicity and apoptosis induction was carried out in MCF-7,HeLa and Saos-2 as cancerous cell lines with different histological origin and human fibroblast served as control normal cell. The cells were treated with different concentrations of chitosan and the cytotoxicity was determined using MTT assay after 24, 48 and 72 h .The mode of death was evaluated by flow cytometry . Results: While both types of chitosan showed significant concentration-dependently cytotoxic effects against the three cancerous cell lines, fibroblast cells showed somehow more compatibility with chitosan. On the other hand, there were no significant differences between LMWC and HMWC cytotoxicity in all cell lines. The flow cytometry results showed the apoptosis pattern of death more in Saos-2 and HeLa while necrosis was more observable with MCF7. Also higher viability with both types of chitosan was seen in fibroblast as normal cells Conclusion: Chitosan shows anticancerous effect against 3 cancerous cell lines, while it is compatible with normal diploid fibroblast cells. Furthermore, it seems that the molecular weight of chitosan does not affect its anticancerous property.

Lemon Juice Mediated Synthesis of 3-Substituted Quinazolin-4(3H)-Ones and their Pharmacological Evaluation

2020 ◽  
Vol 19 (16) ◽  
pp. 2001-2009 ◽  
Author(s):  
Malavattu G. Prasad ◽  
C. Vijaya Lakshmi ◽  
Naresh K. Katari ◽  
Sreekantha B. Jonnalagadda ◽  
Manojit Pal
Keyword(s):  
Cell Line ◽  
Cell Lines ◽  
Hek293 Cell ◽  
Glyoxylic Acid ◽  
Lemon Juice ◽  
Cytotoxic Agents ◽  
Diverse Range ◽  
Hek293 Cell Line ◽  
Three Component Reaction ◽  
Mcf 7

Background: Compounds containing the quinazoline-4(3H)-one framework constitute an important class of fused N-heterocycles that are found in more than 200 naturally occurring alkaloids. These compounds also show a diverse range of pharmacological activities including antitumor properties. This prompted us to explore a series of quinazolin-4-(3H)-one derivatives having no substituent at C-2 as potential cytotoxic agents. Objective: The objective of this study was to synthesize and evaluate 3-substituted quinazolin-4(3H)-one derivatives for their potential cytotoxic properties. Methods: A convenient method has been developed for the rapid synthesis of this class of compounds under a mild and non-hazardous reaction condition in good yields. The methodology involved a three-component reaction employing isatoic anhydride, amines and glyoxylic acid as reactants in the presence of lemon juice in PEG- 400 at room temperature (25-30ºC) under ultrasound irradiation. All the synthesized compounds were screened via an MTT assay for their potential cytotoxic properties in vitro using the cancerous cell lines e.g. A549, A2780, HepG2, K562, MCF-7 and HCT-116 and a non-cancerous HEK293 cell line. Results: Several compounds such as 3a, 3b, 3d, 3e and 3f showed promising growth inhibition against these cancer cell lines but no significant effects on HEK293 cell line. The IC50 values of these compounds were comparable to doxorubicin whereas 3f significantly induced apoptosis in MCF-7 cells that also was comparable to doxorubicin. Conclusion: An ultrasound-assisted MCR facilitated by lemon juice has been developed to synthesize 3- substituted quinazolin-4(3H)-one derivatives that could act as potential anticancer agents.

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