scholarly journals A Multicomponent Protocol for the Synthesis of Highly Functionalized γ-Lactam Derivatives and Their Applications as Antiproliferative Agents

2021 ◽  
Vol 14 (8) ◽  
pp. 782
Author(s):  
Xabier del Corte ◽  
Adrián López-Francés ◽  
Aitor Maestro ◽  
Ilia Villate-Beitia ◽  
Myriam Sainz-Ramos ◽  
...  
Keyword(s):  
Human Tumor ◽  
Human Colon ◽  
In Vitro Cytotoxicity ◽  
Breast Adenocarcinoma ◽  
Cervix Carcinoma ◽  
Synthetic Methodology ◽  
Human Tumor Cell Lines ◽  
Human Prostate Carcinoma ◽  
Human Ovarian Carcinoma

An efficient synthetic methodology for the preparation of 3-amino 1,5-dihydro-2H-pyrrol-2-ones through a multicomponent reaction of amines, aldehydes, and pyruvate derivatives is reported. In addition, the densely substituted lactam substrates show in vitro cytotoxicity, inhibiting the growth of carcinoma human tumor cell lines HEK293 (human embryonic kidney), MCF7 (human breast adenocarcinoma), HTB81 (human prostate carcinoma), HeLa (human epithelioid cervix carcinoma), RKO (human colon epithelial carcinoma), SKOV3 (human ovarian carcinoma), and A549 (carcinomic human alveolar basal epithelial cell). Given the possibilities in the diversity of the substituents that offer the multicomponent synthetic methodology, an extensive structure-activity profile is presented. In addition, both enantiomers of phosphonate-derived γ-lactam have been synthesized and isolated and a study of the cytotoxic activity of the racemic substrate vs. its two enantiomers is also presented. Cell morphology analysis and flow cytometry assays indicate that the main pathway by which our compounds induce cytotoxicity is based on the activation of the intracellular apoptotic mechanism.

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.

Synthesis and Cytotoxicity of New Mannich Bases of 6-[3-(3,4,5-Trimetoxyphenyl)-2- propenoyl]-2(3H)-Benzoxazolone

2020 ◽  
Vol 17 (4) ◽  
pp. 512-517
Author(s):  
Ognyan Ivanov Petrov ◽  
Yordanka Borisova Ivanova ◽  
Mariana Stefanova Gerova ◽  
Georgi Tsvetanov Momekov
Keyword(s):  
Tumor Cell ◽  
Cell Lines ◽  
Biological Activities ◽  
Human Tumor ◽  
Mannich Bases ◽  
In Vitro Cytotoxicity ◽  
Tumor Cell Lines ◽  
Human Tumor Cell ◽  
Human Tumor Cell Lines

Background: Chemotherapy is one of the mainstays of cancer treatment, despite the serious side effects of the clinically available anticancer drugs. In recent years increasing attention has been directed towards novel agents with improved efficacy and selectivity. Compounds with chalcone backbone have been reported to possess various biological activities such as anticancer, antimicrobial, anti-inflammatory, analgesic, antioxidant, etc. It was reported that aminomethylation of hydroxy chalcones to the corresponding Mannich bases increased their cytotoxicity. In this context, our interest has been focused on the design and synthesis of the so-called multi-target molecules, containing two or more pharmacophore fragments. Methods: A series of Mannich bases were synthesized by the reaction between 6-[3-(3,4,5- trimethoxyphenyl)-2-propenoyl]-2(3Н)-benzoxazolone, formaldehyde, and a secondary amine. The structures of the compounds were confirmed by elemental analysis, IR and NMR spectra. The new Mannich bases were evaluated for their in vitro cytotoxicity against a panel of human tumor cell lines, including BV-173, SKW-3, K-562, HL-60, HD-MY-Z and MDA-MB-231. The effects of selected compounds on the cellular levels of glutathione (GSH) were determined. Results: The new compounds 4a-e exhibited concentration-dependent cytotoxic effects at micromolar concentrations in MTT-dye reduction assay against a panel of human tumor cell lines, similar to those of starting chalcone 3. The tested agents led to concentration - dependent depletion of cellular GSH levels, whereby the effects of the chalcone prototype 3 and its Mannich base-derivatives were comparable. Conclusion: The highest chemosensitivity to the tested compounds was observed in BV- 173followed by SKW-3 and HL-60 cell lines.

scholarly journals Synthesis and cytotoxicity of 3-amino-glycyrrhetinic acid derivatives

2018 ◽  
Vol 7 (1) ◽  
pp. 39-55 ◽  
Author(s):  
Martin Sahn ◽  
Anja Grupe ◽  
Lucie Heller ◽  
Hidayat Hussain ◽  
Ahmed Al-Harrasi ◽  
...  
Keyword(s):  
Parent Compound ◽  
Human Tumor ◽  
In Vitro Cytotoxicity ◽  
Glycyrrhetinic Acid ◽  
Human Tumor Cell Lines ◽  
Amino Esters ◽  
Cytotoxic Compound ◽  
Amino Derivatives ◽  
Derivatives Of

The aim of this study was to prepare 3-hydroximino- and 3-amino derivatives of glycyrrhetinic acid and derivatives to evaluate their in vitro cytotoxicity for a panel of human tumor cell lines. Thus, commercially available glycyrrhetinic acid (1) was acetylated or oxidized at position C-3 and transformed into a variety of different esters and amides followed by their conversion to 3-oximes and amines. While the parent compound was not cytotoxic at all, the 3-amino esters are highly cytotoxic. Interestingly, 3-amino amides were significantly less cytotoxic than 3-amino esters. The (3b, 18b, 20b) Benzyl 3-amino-11-oxoolean-12-en-30-oate was the most cytotoxic compound of this series showing an EC50 = 1.3 mM for 518A2 melanoma cells.

In vitro Cytotoxicity of Three 4,9-Diazapyrenium Hydrogensulfate Derivatives on Different Human Tumor Cell Lines

Chemotherapy ◽  
2000 ◽  
Vol 46 (2) ◽  
pp. 143-149 ◽  
Author(s):  
S. Roknić ◽  
Lj. Glavaš-Obrovac ◽  
I. Karner ◽  
I. Piantanida ◽  
M. Žinić ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Cell Lines ◽  
Human Tumor ◽  
In Vitro Cytotoxicity ◽  
Tumor Cell Lines ◽  
Human Tumor Cell ◽  
Human Tumor Cell Lines

scholarly journals Evaluation of Antiproliferative Palladium(II) Complexes of Synthetic Bisdemethoxycurcumin towards In Vitro Cytotoxicity and Molecular Docking on DNA Sequence

Molecules ◽  
2021 ◽  
Vol 26 (14) ◽  
pp. 4369
Author(s):  
Natalia Miklášová ◽  
Peter Herich ◽  
Juan Carlos Dávila-Becerril ◽  
Joaquín Barroso-Flores ◽  
Eva Fischer-Fodor ◽  
...  
Keyword(s):  
Biological Activity ◽  
Colorectal Carcinoma ◽  
Cell Lines ◽  
Biological Activities ◽  
Human Tumor ◽  
Large Family ◽  
In Vitro Cytotoxicity ◽  
Breast Adenocarcinoma ◽  
Human Colorectal Carcinoma

Metallodrugs form a large family of therapeutic agents against cancer, among which is cisplatin, a paradigmatic member. Therapeutic resistance and undesired side effects to Pt(II) related drugs, prompts research on different metal–ligand combinations with potentially enhanced biological activity. We present the synthesis and biological tests of novel palladium(II) complexes containing bisdemethoxycurcumin (BDMC) 1 and 2. Complexes were fully characterized and their structures were determined by X-ray diffraction. Their biological activity was assessed for several selected human tumor cell lines: Jurkat (human leukaemic T-cell lymphoma), HCT-116 (human colorectal carcinoma), HeLa (human cervix epitheloid carcinoma), MCF-7 (human breast adenocarcinoma), MDA-MB-231 (human mammary gland adenocarcinoma), A549 (human alveolar adenocarcinoma), Caco-2 (human colorectal carcinoma), and for non-cancerous 3T3 cells (murine fibroblasts). The cytotoxicity of 1 is comparable to that of cisplatin, and superior to that of 2 in all cell lines. It is a correlation between IC50 values of 1 and 2 in the eight studied cell types, promising a potential use as anti-proliferative drugs. Moreover, for Jurkat cell line, complexes 1 and 2, show an enhanced activity. DFT and docking calculations on the NF-κB protein, Human Serum Albumin (HSA), and DNA were performed for 1 and 2 to correlate with their biological activities.

scholarly journals Synthesis and biological activity evaluation of new functionally substituted 5-arylidene-2,4-dioxotetrahydro-1,3-thiazoles

2006 ◽  
Vol 71 (8-9) ◽  
pp. 861-866 ◽  
Author(s):  
Katarina Popov-Pergal ◽  
Milica Rancic ◽  
Miroslav Pergal ◽  
Gordana Bogdanovic ◽  
Vesna Kojic ◽  
...  
Keyword(s):  
Human Tumor ◽  
Fibroblast Cell ◽  
In Vitro Cytotoxicity ◽  
Normal Lung ◽  
Cholesteryl Esters ◽  
Tumor Cell Lines ◽  
Human Tumor Cell ◽  
Human Tumor Cell Lines ◽  
Lung Fibroblast Cell Line

New functionally substituted 5-arylidene-2,4-dioxotetrahydro 1,3-thiazole- 3-carboxylic acid cholesteryl esters were synthesized from 2,4-dioxotetrahydro- 1,3-thiazole and evaluated for their in vitro cytotoxicity against several human tumor cell lines and one normal lung fibroblast cell line.

scholarly journals Synthesis, Spectroscopic Characterization, Structural Studies, and In Vitro Antitumor Activities of Pyridine-3-carbaldehyde Thiosemicarbazone Derivatives

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Wilfredo Hernández ◽  
Fernando Carrasco ◽  
Abraham Vaisberg ◽  
Evgenia Spodine ◽  
Jorge Manzur ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Cell Lines ◽  
Human Tumor ◽  
Breast Adenocarcinoma ◽  
Significant Activity ◽  
Tumor Cell Lines ◽  
Human Tumor Cell ◽  
Human Tumor Cell Lines ◽  
Biological Studies

Eight new thiosemicarbazone derivatives, 6-(1-trifluoroethoxy)pyridine-3-carbaldehyde thiosemicarbazone (1), 6-(4′-fluorophenyl)pyridine-3-carbaldehyde thiosemicarbazone (2), 5-chloro-pyridine-3-carbaldehyde thiosemicarbazone (3), 2-chloro-5-bromo-pyridine-3-carbaldehyde thiosemicarbazone (4), 6-(3′,4′-dimethoxyphenyl)pyridine-3-carbaldehyde thiosemicarbazone (5), 2-chloro-5-fluor-pyridine-3-carbaldehyde thiosemicarbazone, (6), 5-iodo-pyridine-3-carbaldehyde thiosemicarbazone (7), and 6-(3′,5′-dichlorophenyl)pyridine-3-carbaldehyde thiosemicarbazone (8) were synthesized, from the reaction of the corresponding pyridine-3-carbaldehyde with thiosemicarbazide. The synthesized compounds were characterized by ESI-Mass, UV-Vis, IR, and NMR (1H, 13C, 19F) spectroscopic techniques. Molar mass values and spectroscopic data are consistent with the proposed structural formulas. The molecular structure of 7 has been also confirmed by single crystal X-ray diffraction. In the solid state 7 exists in the E conformation about the N2-N3 bond; 7 also presents the E conformation in solution, as evidenced by 1H NMR spectroscopy. The in vitro antitumor activity of the synthesized compounds was studied on six human tumor cell lines: H460 (lung large cell carcinoma), HuTu80 (duodenum adenocarcinoma), DU145 (prostate carcinoma), MCF-7 (breast adenocarcinoma), M-14 (amelanotic melanoma), and HT-29 (colon adenocarcinoma). Furthermore, toxicity studies in 3T3 normal cells were carried out for the prepared compounds. The results were expressed as IC50 and the selectivity index (SI) was calculated. Biological studies revealed that 1 (IC50 = 3.36 to 21.35 μM) displayed the highest antiproliferative activity, as compared to the other tested thiosemicarbazones (IC50 = 40.00 to >582.26 μM) against different types of human tumor cell lines. 1 was found to be about twice as cytotoxic (SI = 1.82) than 5-fluorouracile (5-FU) against the M14 cell line, indicating its efficiency in inhibiting the cell growth even at low concentrations. A slightly less efficient activity was shown by 1 towards the HuTu80 and MCF7 tumor cell lines, as compared to that of 5-FU. Therefore, 1 can be considered as a promising candidate to be used as a pharmacological agent, since it presents significant activity and was found to be more innocuous than the 5-FU anticancer drug against the 3T3 mouse embryo fibroblast cells.

Novel Symmetrical 1,4-Disubstituted-bis-1,2,3-Triazoles: Synthesis by Double CuAAC and Cytotoxicity Evaluation

2018 ◽  
Vol 18 (17) ◽  
pp. 1475-1482 ◽  
Author(s):  
Wallace J. Reis ◽  
Paulo O.L. Moreira ◽  
Rosemeire B. Alves ◽  
Heloísa H.M. Oliveira ◽  
Luciana M. Silva ◽  
...  
Keyword(s):  
Cell Lines ◽  
Human Tumor ◽  
Breast Adenocarcinoma ◽  
Tetraethylene Glycol ◽  
Ovarian Adenocarcinoma ◽  
Standard Drug ◽  
Human Tumor Cell Lines ◽  
Induced Apoptosis ◽  
Brdu Assay

Background: A series of symmetrical 1,4-disubstituted bis-1,2,3-triazoles was prepared by double copper catalyzed Azide-alkyne Cycloaddition (CuAAC) from aliphatic bis-azides and a tetraethylene glycol bis-azide derivative. The eighteen novel compounds were evaluated in vitro for their cytotoxic activity against two human tumor cell lines: Human breast adenocarcinoma (MDA-MB 231) and ovarian adenocarcinoma (TOV-21G). Results and Conclusion: The results of colorimetric MTT assays showed that compounds 4j and 4q exhibited a better selectivity index and cell viability comparable with the standard drug doxorubicin. These compounds induced apoptosis in both tested cell lines, as assessed by BrdU assay. The results suggest that these structurally simple compounds may be promising prototypes for antitumoral agents.

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