Synthesis of 2-Substituted 4-Arylidene-5(4H)-oxazolones as Potential Cytotoxic Agents in the Presence of Lemon Juice as a Biocatalyst

2020 ◽  
Vol 22 (9) ◽  
pp. 625-634 ◽  
Author(s):  
Malavattu G. Prasad ◽  
Chapala V. Lakshmi ◽  
Naresh K. Katari ◽  
Krishnan Anand ◽  
Manojit Pal ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Line ◽  
Anticancer Agents ◽  
Human Colon ◽  
Malignant Cell ◽  
Lemon Juice ◽  
Cytotoxic Agents ◽  
Reference Drug ◽  
Initial Objective

Background: The oxazolone class of compounds is known to exert a profound effect on malignant cell proliferation, tumor angiogenesis and /or on the established neoplastic vasculature. Additionally, these compounds are generally known to have a low tendency to interact with DNA which is not common with most of the conventional cytotoxic agents. Thus, this class of compounds is of particular interest for the discovery and development of patient-friendly anticancer agents. Objective: The initial objective of this study was to synthesize and evaluate 2-substituted 4-arylidene- 5(4H)-oxazolones for their potential anticancer properties. Methods: A simple, mild and non-hazardous synthetic methodology has been developed for the preparation of 2-substituted 4-arylidene-5(4H)-oxazolones. The methodology involved lemon juice mediated condensation of N-acyl glycine derivatives including hippuric acid with arylaldehydes in PEG-400 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. K562 (human chronic myeloid leukemia), Colo-205 (human colon carcinoma), and A549 (human lung carcinoma) and a non-cancerous HEK293 (human embryonic kidney) cell line. Results: Compounds 3a, 3c and 3i showed promising growth inhibition against A549 cell line but no significant effects on HEK293 cell line, indicating their selectivity towards cancer cells. Moreover, their IC50 values suggested that all these compounds were comparable to the reference drug doxorubicin indicating their potential against lung cancer. Conclusion: he 4-arylidene-5(4H)-oxazolone framework presented here could be a new template for the design and discovery of potential anticancer agents especially for lung cancer.

scholarly journals Identification of Ent-Kaurane Diterpenoid Compounds as Potential Inhibitors of the PI3K Pathway in Nonsmall Cell Lung Cancer Through Molecular Docking Simulations

2021 ◽  
Vol 16 (9) ◽  
pp. 1934578X2110332
Author(s):  
Pham T. Hong Minh ◽  
Tran T. Hoai Van ◽  
Tran Q. Toan ◽  
Le M. Bui ◽  
Nguyen H. Thuan Anh ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Molecular Docking ◽  
Cell Lung Cancer ◽  
Anticancer Agents ◽  
Nonsmall Cell Lung Cancer ◽  
Molecular Docking Study ◽  
Vitro Assay ◽  
Reference Drug ◽  
Docking Simulations

Annual mortality of 8.2 million could be attributable to cancer globally, posing a serious health issue; particularly, the high number of nonsmall cell lung cancer (NSCLC) diagnosed cases in recent years highlight the need for development in anticancer agents. In NSCLC, a number of specific inhibitors of phosphatidylinositol-3-kinase (PI3K), Protein kinase B (AKT), and mammalian target of rapamycin are currently under development; however, the early evidence has yielded disappointing results. Ent-kaurane diterpenoid compounds from Cronton tonkinensis have been investigated for several bioactivities such as antibacterial, cytotoxic activity, and so on;; however, lung cancer is not yet studied. In this study, we conducted a molecular docking study of 7 ent-kaurane diterpenoids from C tonkinensis against PI3K targeted anticancer therapies; furthermore, their cytotoxicity effects against A549 lung cancer cells were also evaluated. Obtained results indicated that compounds 7, 6, 2, and 1 exhibited significant inhibitory results in comparison to the reference drug oxaliplatin which suggests further in vitro assay for drug development.

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.

Design, Synthesis, In vitro and In silico Evaluation of New Hydrazonebased Antitumor Agents as Potent Akt Inhibitors

2020 ◽  
Vol 17 (11) ◽  
pp. 1380-1392
Author(s):  
Emine Merve Güngör ◽  
Mehlika Dilek Altıntop ◽  
Belgin Sever ◽  
Gülşen Akalın Çiftçi
Keyword(s):  
Cell Line ◽  
Anticancer Agents ◽  
In Silico ◽  
Antitumor Agents ◽  
Colorimetric Assay ◽  
Fibroblast Cell ◽  
Lipinski’S Rule ◽  
In Silico Docking ◽  
Embryonic Fibroblast

Background: Akt is overexpressed or activated in a variety of human cancers, including gliomas, lung, breast, ovarian, gastric and pancreatic carcinomas. Akt inhibition leads to the induction of apoptosis and inhibition of tumor growth and therefore extensive efforts have been devoted to the discovery of potent antitumor drugs targeting Akt. Objectives: The objective of this work was to identify potent anticancer agents targeting Akt. Methods: New hydrazone derivatives were synthesized and investigated for their cytotoxic effects on 5RP7 H-ras oncogene transformed rat embryonic fibroblast and L929 mouse embryonic fibroblast cell lines. Besides, the apoptotic effects of the most active compounds on 5RP7 cell line were evaluated using flow cytometry. Their Akt inhibitory effects were also investigated using a colorimetric assay. In silico docking and Absorption, Distribution, Metabolism and Excretion (ADME) studies were also performed using Schrödinger’s Maestro molecular modeling package. Results and Discussion: Compounds 3a, 3d, 3g and 3j were found to be effective on 5RP7 cells (with IC50 values of <0.97, <0.97, 1.13±0.06 and <0.97 μg/mL, respectively) when compared with cisplatin (IC50= 1.87±0.15 μg/mL). It was determined that these four compounds significantly induced apoptosis in 5RP7 cell line. Among them, N'-benzylidene-2-[(4-(4-methoxyphenyl)pyrimidin- 2-yl)thio]acetohydrazide (3g) significantly inhibited Akt (IC50= 0.5±0.08 μg/mL) when compared with GSK690693 (IC50= 0.6±0.05 μg/mL). Docking studies suggested that compound 3g showed good affinity to the active site of Akt (PDB code: 2JDO). According to in silico ADME studies, the compound also complies with Lipinski's rule of five and Jorgensen's rule of three. Conclusion: Compound 3g stands out as a potential orally bioavailable cytotoxic agent and apoptosis inducer targeting Akt.

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.

scholarly journals Synthesis and Experimental Validation of New Designed Heterocyclic Compounds with Antiproliferative Activity versus Breast Cancer Cell Lines MCF-7 and MDA-MB-231

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Vincenza Barresi ◽  
Carmela Bonaccorso ◽  
Domenico A. Cristaldi ◽  
Maria N. Modica ◽  
Nicolò Musso ◽  
...  
Keyword(s):  
Cell Line ◽  
Cell Lines ◽  
Cancer Cell ◽  
Anticancer Agents ◽  
Cancer Cell Line ◽  
Breast Cancer Cell Lines ◽  
Design And Synthesis ◽  
Human Breast Cell ◽  
Mcf 7

Recent drug discovery efforts are highly focused towards identification, design, and synthesis of small molecules as anticancer agents. With this aim, we recently designed and synthesized novel compounds with high efficacy and specificity for the treatment of breast tumors. Based on the obtained results, we constructed a Volsurf+ (VS+) model using a dataset of 59 compounds able to predict the in vitro antitumor activity against MCF-7 cancer cell line for new derivatives. In the present paper, in order to further verify the robustness of this model, we report the results of the projection of more than 150 known molecules and 9 newly synthesized compounds. We predict their activity versus MCF-7 cell line and experimentally verify the in silico results for some promising chosen molecules in two human breast cell lines, MCF-7 and MDA-MB-231.

scholarly journals Sinoporphyrin Sodium-Mediated Sonodynamic Therapy Inhibits RIP3 Expression and Induces Apoptosis in the H446 Small Cell Lung Cancer Cell Line

2018 ◽  
Vol 51 (6) ◽  
pp. 2938-2954 ◽  
Author(s):  
Jing Shen ◽  
Shoubo Cao ◽  
Xin Sun ◽  
Bo Pan ◽  
Jingyan Cao ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Line ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Cell Counting ◽  
Small Cell Lung ◽  
Sonodynamic Therapy

Background/Aims: Sonodynamic therapy (SDT) is expected to be a new method to solve the clinical problems caused by advanced metastasis in patients with lung cancer. The use of ultrasound has the advantage of being noninvasive, with deep-penetration properties. This study explored the anti-tumor effect of SDT with a new sonosensitizer, sinoporphyrin sodium (DVDMS), on the human small cell lung cancer H446 cell line in vitro and in vivo. Methods: Absorption of DVDMS was detected by a fluorescence spectrophotometer, and DVDMS toxicity was determined using a Cell Counting Kit-8. Mitochondrial membrane potential (MMP) was assessed using the JC-1 fluorescent probe. Cell apoptosis was measured by flow cytometry, and apoptosis-related proteins were detected by western blotting. The expression of cytokines was measured using an enzyme-linked immunosorbent assay and quantitative real-time PCR. To verify the in vitro results, we detected tumor volumes and weight changes in a xenograft nude mouse model after DVDMS-SDT. Hematoxylin and eosin staining was used to observe changes to the tumor, heart, liver, spleen, lung, and kidney of the mice, and immunohistochemistry was used to examine changes in the expression of tumor CD34 and receptor-interacting protein kinase-3 (RIP3), while terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling was used to observe apoptosis in tumor tissues. Results: DVDMS-SDT-treated H446 cells increased the rate of cellular apoptosis and the levels of reactive oxygen species (ROS), cleaved caspase-3, cleaved caspase-8, cleaved caspase-9, and caspase-10, and decreased the levels of MMP, RIP3, B-cell lymphoma 2, vascular endothelial growth factor, and tumor necrosis factor-α. The sonotoxic effect was mediated by ROS and was reduced by a ROS scavenger (N-acetyl-L-cysteine). In the in vivo mouse xenograft model, DVDMS-SDT showed efficient anti-cancer effects with no visible side effects. Conclusion: DVDMS-SDT induced apoptosis in H446 cells, in part by targeting mitochondria through the mitochondria-mediated apoptosis signaling pathway, and the extrinsic apoptosis pathway was also shown to be involved. Both apoptosis and changes in RIP3 expression were closely related to the generation of ROS. DVDMS-SDT will be advantageous for the management of small cell lung cancer due to its noninvasive characteristics.

scholarly journals Synthesis of Some Polysubstituted Nicotinonitriles and Derived Pyrido[2,3-d]pyrimidines asIn VitroCytotoxic and Antimicrobial Candidates

2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Hassan M. Faidallah ◽  
Sherif A. F. Rostom ◽  
Khalid A. Khan
Keyword(s):  
Cell Line ◽  
Colon Carcinoma ◽  
Human Tumor ◽  
Human Colon ◽  
Pyrimidine Ring ◽  
Inhibitory Effect ◽  
Breast Adenocarcinoma ◽  
Human Tumor Cell Lines ◽  
E Coli

The synthesis of polysubstituted pyridines, in addition to some derived pyrido[2,3-d]pyrimidine ring systems supported with chemotherapeutically active functionalities, is described. They were evaluated for theirin vitrocytotoxic effects against three different human tumor cell lines (human colon carcinoma HT29, hepatocellular carcinoma Hep-G2, and Caucasian breast adenocarcinoma MCF7). Nine compounds displayed variable cytotoxic potential, among which alkylthio analogs33,34, and37emerged as the most active members, being almost twice as active as doxorubicin against the colon carcinoma HT29 cell line. In addition, the same three analogs showed a clear differential cytotoxic profile as they exhibited a marginal inhibitory effect on the growth of the normal nontransformed human foreskin fibroblast Hs27 cell line. Meanwhile, nineteen compounds were able to exhibit significant antibacterial activity against both Gram-positive and Gram-negative bacteria, together with moderate antifungal activities. The pyrido[2,3-d]pyrimidine-2(1H)-thione30together with its alkylthio derivatives33and34stemmed as the most active antimicrobial members being equipotent to ampicillin againstS. aureus,E. coli,andP. aeruginosa,together with a noticeable antifungal activity againstC. albicans.Compounds33and34could be considered as a promising template for possible dual antimicrobial-anticancer candidates.

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