Ultrasound-assisted Synthesis of 6-substituted indolo[2,3-b]quinolines: their Evaluation as Potential Cytotoxic Agents

2019 ◽  
Vol 19 (7) ◽  
pp. 599-608
Author(s):  
Nagaraju Marepu ◽  
Mahesh Gosi ◽  
Santhoshi Sumana Vedula ◽  
Sunandamma Yeturu ◽  
Manojit Pal
Keyword(s):  
Cell Lines ◽  
Anticancer Agents ◽  
Hek293 Cell ◽  
Mcf7 Cell ◽  
Cytotoxic Agents ◽  
Mcf7 Cells ◽  
Pharmacological Activities ◽  
Bond Forming ◽  
Ultrasound Assisted

<p>Background: The indolo[2,3-b]quinoline framework is often found in various natural products displaying a range of pharmacological activities. This is an attractive template for the design and discovery of potential drugs especially for the identification of new anticancer agents. Methods: The synthesis of 6-substituted indolo[2,3-b]quinolones was undertaken and carried out using a ultrasound assisted method involving two sequential C-N bond forming reactions between 3-(2- bromophenyl)-2-chloroquinoline and amines in a single pot in the presence of Pd(OAc)2 and a ligand (S)-BINAP. All the synthesized compounds were tested in vitro against two cancer cell lines e.g. MCF7 and HepG2 along with non-cancerous HEK293 cell lines. Results: Two of these compounds showed promising and selective growth inhibition of MCF7 cell lines and one induced significant apoptosis in cancer (MCF7) cells. Conclusion: Compounds based on indolo[2,3-b]quinolone framework may be useful for the identification of new cytotoxic agents thereby potential cure for breast cancer.</p>

Lemon Juice Mediated Reaction under Ultrasound Irradiation: Synthesis of Indolofuroquinoxalines as Potential Anticancer Agents

2019 ◽  
Vol 19 (8) ◽  
pp. 671-678 ◽  
Author(s):  
Gutta Lakshmi Prasanna ◽  
Bodapati Veera Durga Rao ◽  
Alugubelli Gopi Reddy ◽  
Mandava V. Basaveswara Rao ◽  
Manojit Pal
Keyword(s):  
Cell Line ◽  
Cell Lines ◽  
Anticancer Agents ◽  
Hek293 Cell ◽  
Mcf7 Cell ◽  
Ultrasound Irradiation ◽  
Lemon Juice ◽  
Anticancer Properties ◽  
Hek293 Cell Line

Background: A non-hazardous synthetic methodology has been developed for the preparation of compounds based on indolofuroquinoxaline framework. Lemon juice that is known to play the role of a biocatalyst in various organic reactions was used for this purpose. Method: A number of indolofuroquinoxaline derivatives were prepared via the lemon juice mediated condensation of methyl 2-(2-chloro-1H-indol-3-yl)-2-oxoacetate or its N-alkyl derivatives with 1,2- diamines under ultrasound irradiation. All the synthesized compounds were screened via an MTT assay for their potential anticancer properties in vitro using a number of cancer cell lines including MDA-MB 231, and MCF7, K562, Colo-205 and IMR-32 and the non-cancerous HEK293 cell line. Compounds 3a, 3b and 3c showed promising growth inhibition against K562, MDA-MB 231 and MCF7 cell lines but no significant effects on HEK293 cell line suggesting their selectivity towards cancer cells. Results and Conclusion: Moreover, according to their IC50 values, all these compounds appeared to be relatively more potent towards K562 cell line over MDA-MB 231 and MCF7 cell lines indicating their potential against leukemia.

scholarly journals Synthesis and In Silico Docking of New Pyrazolo[4,3-e]pyrido[1,2-a]pyrimidine-based Cytotoxic Agents

2021 ◽  
Vol 22 (19) ◽  
pp. 10258
Author(s):  
Mabrouk Horchani ◽  
Niels V. Heise ◽  
Sophie Hoenke ◽  
René Csuk ◽  
Abdel Halim Harrath ◽  
...  
Keyword(s):  
Cell Lines ◽  
Anticancer Agents ◽  
In Silico ◽  
Human Tumor ◽  
In Vitro Cytotoxicity ◽  
Cytotoxic Agents ◽  
Hek293 Cells ◽  
Binding Interaction ◽  
In Silico Docking

To explore a new set of anticancer agents, a novel series of pyrazolo[4,3-e]pyrido[1,2-a]pyrimidine derivativeshave been designed and synthesized viacyclocondensation reactions of pyrazolo-enaminone with a series of arylidenemalononitriles; compound 5 was obtained from 5-amino-4-cyanopyrazole. The structures of the target compounds were investigated by spectral techniques and elemental analysis (IR, UV–Vis, 1H NMR, 13C NMR and ESI-MS). All compounds were evaluated for their in vitro cytotoxicity employing a panel of different human tumor cell lines, A375, HT29, MCF7, A2780, FaDu as well as non-malignant NIH 3T3 and HEK293 cells. It has been found that the pyrazolo-pyrido-pyrimidine analog bearing a 4-Br-phenyl moiety was the most active toward many cell lines with EC50 values ranging between 9.1 and 13.5 µM. Moreover, in silico docking studies of the latter with six anticancer drug targets, i.e., DHFR, VEGFR2, HER-2/neu, hCA-IX, CDK6 and LOX5, were also performed, in order to gain some insights into their putative mode of binding interaction and to estimate the free binding energy of this bioactive molecule.

scholarly journals Synthesis and In Silico Docking of New Pyrazolo[4,3-e]Pyrido[1,2-a]Pyrimidine-Based Cytotoxic Agents

2021 ◽  
Author(s):  
Mabrouk Horchani ◽  
Niels V. Heise ◽  
Sophie Hoenke ◽  
Rene Csuk ◽  
Abdel Halim Harrath ◽  
...  
Keyword(s):  
Cell Lines ◽  
Anticancer Agents ◽  
In Silico ◽  
Human Tumor ◽  
In Vitro Cytotoxicity ◽  
Cytotoxic Agents ◽  
Hek293 Cells ◽  
Binding Interaction ◽  
In Silico Docking

To explore a new set of anticancer agents, a novel series of pyrazolo[4,3-e]pyrido[1,2-a]pyrimidine derivatives 7a-l have been designed and synthesized via cyclocondensation reactions of pyrazolo-enaminone 5 with a series of arylidene malononitriles; compound 5 was obtained from 5-amino-4-cyanopyrazole (3). The structures of the target compounds 7a-l were investigated by spectral techniques and elemental analysis (IR, UV-Vis, 1H NMR, 13C NMR and ESI-MS). All compounds were evaluated for their in vitro cytotoxicity employing a panel of different human tumor cell lines, A375, HT29, MCF7, A2780, FaDu as well as non-malignant NIH 3T3 and HEK293 cells. It has been found that the conjugate 7e was the most active towards many cell lines with EC50 values ranging between 9.1 and 13.5 &micro;M, respectively. Moreover, in silico docking studies of 7e with six anticancer drug targets, i.e. DHFR, VEGFR2, HER-2/neu, hCA-IX, CDK6 and LOX also was performed, in order to gain some insights into their putative mode of binding interaction and to estimate the free binding energy of this bioactive molecule.

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.

Triarylpyrazole Derivatives as Potent Cytotoxic Agents; Synthesis and Bioactivity Evaluation “Pyrazole Derivatives as Anticancer Agent”

Drug Research ◽  
2021 ◽  
Author(s):  
Bilqees Sameem ◽  
Ebrahim Saeedian Moghadam ◽  
Majid Darabi ◽  
Zahra Shahsavari ◽  
Mohsen Amini
Keyword(s):  
Cell Lines ◽  
Anticancer Agents ◽  
Human Cancer ◽  
Carcinoma Cells ◽  
Cytotoxic Agents ◽  
Cancer Drug ◽  
Pyrazole Derivatives ◽  
Anti Cancer ◽  
Ht 29

Abstract Background During the last recent years, several anti-cancer agents were introduced for the treatment of diverse kinds of cancer. Despite their potential in the treatment of cancer, drug resistance and adverse toxicity such as peripheral neuropathy are some of the negative criteria of anti-cancer agents and for this reason, the design and synthesis of new anti-cancer agents are important. Objective Design, synthesis, and anticancer activity evaluation of some pyrazole derivatives. Methods A series of Target compounds were prepared using multistep synthesis. Their cytotoxic activity against three different human cancer cell lines namely human colon carcinoma cells (HT-29), epithelial carcinoma cells (U-87MG), pancreatic cancerous cells (Panc-1) as well as AGO1522 normal cell line using in vitro 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay was investigated. Results 1,3-Diaryl-5-(3,4,5-trimethoxyphenyl)-4,5-dihydro-1H-pyrazole and 1,3-Diaryl-5-(3,4,5-trimethoxyphenyl)- 1H-pyrazole were synthesized in good yields and their structure and purity were confirmed using 1H-NMR, 13C-NMR, and elemental analysis. Generally, the synthesized scaffolds exhibited good cytotoxicity against cancerous cell lines in comparison to the reference standard, paclitaxel. Compounds 3a and 3c, in Annexin V/ PI staining assay, exerted remarkable activity in apoptosis induction in HT-29 cell lines. Both of them also led to cell cycle arrest in the sub-G1 phase which is inconsistent with the results of apoptosis assay. Conclusion Concerning obtained results, it is interesting to synthesis more pyrazole derivatives as anticancer agents.

In Vitro Antitumor Evaluation of Acrylic Acid Derivatives Bearing Quinolinone Moiety as Novel Anticancer Agents

2021 ◽  
Vol 21 ◽  
Author(s):  
Islam Zaki ◽  
Sarah A. Eid ◽  
Mohamed S. Elghareb ◽  
Al-Shimaa M. Abas ◽  
Fatten Z. Mohammed ◽  
...  
Keyword(s):  
Acrylic Acid ◽  
Cell Lines ◽  
Cancer Cell ◽  
Anticancer Agents ◽  
Cancer Cell Lines ◽  
Cytotoxic Agents ◽  
Hct 116 ◽  
Emergence Of Resistance ◽  
Further Development

Background: Due to the emergence of resistance to available anticancer agents, the demand for new cytotoxic agents has grown. Objective: This study aims at synthesis and cytotoxic evaluation of new acrylic acid derivatives bearing quinolinone and halogenated quinolinone derivatives against three cancer cell lines. Methods: New acrylic acid derivatives bearing quinolinone and halogenated quinolinone moieties were synthesized and screened for their cytotoxic activity against breast MCF-7, liver HepG2, and colon HCT-116 cancer cell lines. Conclusion: Acrylic acid derivatives bearing quinolinone and halogenated quinolinone moieties represent an important core and could be used as a lead for further development of drug compounds in order to achieve promising therapeutic results.

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.

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.

Evaluation of Pyrano[3,2 C] Quinoline Analogues as Anticancer Agents

2019 ◽  
Vol 19 (10) ◽  
pp. 1285-1292 ◽  
Author(s):  
Kuldip D. Upadhyay ◽  
Anamik K. Shah
Keyword(s):  
Anticancer Agents ◽  
Human Cancer ◽  
Biological Activities ◽  
Cytotoxic Agents ◽  
Tumor Growth Inhibition ◽  
Mice Model ◽  
One Pot ◽  
Aryl Ring ◽  
Hct 116

Background: Quinoline analogues exhibited diversified biological activities depending on the structure type. A number of natural products with pyrano[3,2-c]quinolone structural motifs and patented chromenes were reported as promising cytotoxic agents. Objective: The present study is aimed to evaluate a new series of pyrano[3,2-c]quinoline scaffolds derived from the fusion of bioactive quinolone pharmacophore with structurally diverse aryl substituted chromene for its cytotoxicity. Methods: A library of pyrano[3,2-c]quinoline analogues was prepared from one-pot multi component synthesis using various aromatic aldehydes, malononitrile and 2,4-dihydroxy-1-methylquinoline. The new synthetics were primarily screened for its cytotoxicity (IC50) against different human cancer cell lines in vitro. The promising synthetics were further evaluated in vitro for their potency against different kinase activity. The promising compounds were finally tested for their in vivo efficacy in SCID type mice HCT-116 tumor model. Results: The screening results revealed that compounds 4c, 4f, 4i and 4j showed promising activity in in vitro study. However, compound 4c was found to be the most potent candidate with 23% tumor growth inhibition in HCT-116 tumor mice model. Conclusion: The structure activity relationship suggested that 3-substitution on the aryl ring at C4 position of the pyrano[3,2 c]quinolone moiety seems to have an important position for cytotoxicity activity. However, 3- chloro substitution at C4 aryl ring showed a significant alteration of the bioactive conformer of the parent scaffold and outcome with compound 4c as the most potent candidate of the series.

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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