scholarly journals Stereoselective Synthesis of the Di-Spirooxindole Analogs Based Oxindole and Cyclohexanone Moieties as Potential Anticancer Agents

Molecules ◽  
2021 ◽  
Vol 26 (20) ◽  
pp. 6305
Author(s):  
Abdullah Mohammed Al-Majid ◽  
M. Ali ◽  
Mohammad Shahidul Islam ◽  
Saeed Alshahrani ◽  
Abdullah Saleh Alamary ◽  
...  
Keyword(s):  
Anticancer Activity ◽  
Cell Line ◽  
Cell Lines ◽  
Cancer Cell ◽  
Anticancer Agents ◽  
Stereoselective Synthesis ◽  
Cancer Cell Lines ◽  
Azomethine Ylides ◽  
Active Member ◽  
One Pot

A new series of di-spirooxindole analogs, engrafted with oxindole and cyclohexanone moieties, were synthesized. Initially, azomethine ylides were generated via reaction of the substituted isatins 3a–f (isatin, 3a, 6-chloroisatin, 3b, 5-fluoroisatin, 3c, 5-nitroisatin, 3d, 5-methoxyisatin, 3e, and 5-methylisatin, 3f, and (2S)-octahydro-1H-indole-2-carboxylic acid 2, in situ azomethine ylides reacted with the cyclohexanone based-chalcone 1a–f to afford the target di-spirooxindole compounds 4a–n. This one-pot method provided diverse structurally complex molecules, with biologically relevant spirocycles in a good yields. All synthesized di-spirooxindole analogs, engrafted with oxindole and cyclohexanone moieties, were evaluated for their anticancer activity against four cancer cell lines, including prostate PC3, cervical HeLa, and breast (MCF-7, and MDA-MB231) cancer cell lines. The cytotoxicity of these di-spirooxindole analogs was also examined against human fibroblast BJ cell lines, and they appeared to be non-cytotoxic. Compound 4b was identified as the most active member of this series against prostate cancer cell line PC3 (IC50 = 3.7 ± 1.0 µM). The cyclohexanone engrafted di-spirooxindole analogs 4a and 4l (IC50 = 7.1 ± 0.2, and 7.2 ± 0.5 µM, respectively) were active against HeLa cancer cells, whereas NO2 substituted isatin ring and meta-fluoro-substituted (2E,6E)-2,6-dibenzylidenecyclohexanone containing 4i (IC50 = 7.63 ± 0.08 µM) appeared to be a promising agent against the triple negative breast cancer MDA-MB231 cell line. To explore the plausible mechanism of anticancer activity of di-spirooxindole analogs, molecular docking studies were investigated which suggested that spirooxindole analogs potentially inhibit the activity of MDM2.

scholarly journals Regio- and Stereoselective Synthesis of a New Series of Spirooxindole Pyrrolidine Grafted Thiochromene Scaffolds as Potential Anticancer Agents

Symmetry ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1426
Author(s):  
Assem Barakat ◽  
Mohammad Islam ◽  
M. Ali ◽  
Abdullah Al-Majid ◽  
Saeed Alshahrani ◽  
...  
Keyword(s):  
Cell Line ◽  
Cell Lines ◽  
Cancer Cell ◽  
Anticancer Agents ◽  
Stereoselective Synthesis ◽  
Cancer Cell Lines ◽  
Azomethine Ylides ◽  
Breast Cancer Cell Lines ◽  
Active Member ◽  
Mcf 7

A series of new spiro-heterocycles engrafted spirooxindole/pyrrolidine/thiochromene scaffolds was synthesized by the three-component 1,3-dipolar cycloaddition reactions in a fully controlled regio- and stereo-selective fashion. Condensation of several substituted isatin derivatives with L-proline generated the azomethine ylides which subsequently reacted with chalcones based thiochromene scaffold, and finally afforded the target spiro-compounds. This simple protocol furnished a structurally complex, biologically relevant spiro-heterocycles in good yields through a one-pot process. All synthesized chalcone-based thiochromene, along with the spirooxindole/pyrrolidine/thiochromene scaffolds, were tested for their anticancer activity against four cancer cell lines (PC3, HeLa, MCF-7, and MDA-MB231). Toxicity of these compounds was also evaluated against human fibroblast BJ cell line, and they appeared to be not cytotoxic. For the prostate cancer (PC3) cell line, the most active hybrid, among synthesized series, was compound (7f,IC50 = 8.7 ± 0.7 µM). The most potent spirooxindole/pyrrolidine/thiochromene hybrid against cervical (HeLa) cancer cells was compound (7k, IC50 = 8.4 ± 0.5 µM) having chlorine and p-trifluoromethyl substituents attached to phenyl rings. Finally, against the MCF-7 and MDA-MB231 breast cancer cell lines, compound (7d) was the most active member of this series (IC50 = 7.36 ± 0.37, and 9.44 ± 0.32 µM, respectively).

scholarly journals Synergistic activity of Hsp90 inhibitors and anticancer agents in pancreatic cancer cell cultures

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Simonas Daunys ◽  
Daumantas Matulis ◽  
Vilma Petrikaitė
Keyword(s):  
Pancreatic Cancer ◽  
Anticancer Activity ◽  
Cell Line ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cell Cultures ◽  
Anticancer Agents ◽  
Pancreatic Cancer Cell ◽  
Cancer Cell Lines ◽  
Synergistic Activity

Abstract Heat shock protein 90 (Hsp90) is a widely investigated target for anticancer therapy. The experimental Hsp90 inhibitors ICPD47 and ICPD62 demonstrated anticancer activity against colorectal, osteosarcoma and cervical cancer cell lines. However, their anticancer activity has not been investigated against pancreatic cancer cell lines yet, and there are no data about synergistic activity of these compounds in combination with clinically used anticancer agents. Pancreatic cancer cell lines, MIA PaCa-2 and PANC-1 were exposed to ICPD47 and ICPD62 alone and in combinations with antimetabolites gemcitabine (GEM), 5-fluorouracil (5-FU) and topoisomerase inhibitor doxorubicin (DOX). Effects on cell viability were determined by MTT assay. The synergistic activity was evaluated using Chou-Talalay method. Also, 3D cell cultures were formed using 3D Bioprinting method and the activity of each compound and their combinations was examined by measuring the size change of spheroids. The strongest synergistic activities were determined in combinations using all ratios of ICPD47 with GEM and ICPD62 with GEM in MIA PaCa-2 cell line (combination index <0.5). The combinations of ICPD47 with 5-FU and ICPD47 with GEM in a ratio of 1:5 showed the greatest effect on tumour spheroid growth in both cell lines. The ICPD47 in combination with mild hyperthermia showed significant results, where the EC50 value in PANC-1 cell line dropped from 4.04 ± 0.046 to 1.68 ± 0.004 µM. The ICPD47 and ICPD62 under the same conditions could act synergistically with GEM, 5-FU and DOX and is worth of further investigations, and studies of synergistic effect is a promising path for more efficient anticancer therapies.

scholarly journals Synthesis and cytotoxicity of novel oxindoles dispiro derivatives with thiohydantoin and adamantane fragments

2019 ◽  
Author(s):  
Maxim E Kukushkin ◽  
Dmitriy A Skvortsov ◽  
Marina A Kalinina ◽  
Viktor A Tafeenko ◽  
Vladimir V Burmistrov ◽  
...  
Keyword(s):  
Anticancer Activity ◽  
Cell Line ◽  
Cell Lines ◽  
Cancer Cell ◽  
A549 Cell ◽  
Azomethine Ylides ◽  
Dipolar Cycloaddition ◽  
A549 Cell Line ◽  
One Pot ◽  
P53 Activation

An effective and highly regio- and diastereoselective one-pot synthesis of two type of dispiro heterocyclic systems (2-thioxodispiro[imidazolidine-4,3'-pyrrolidine-2',3''-indoline]-2'',5-diones and 2-thioxodispiro[imidazolidine-4,3'-pyrrolidine-4',3''-indoline]-2'',5-diones) comprising pyrrolidinyloxindole, thiohydantoin and adamantane moieties have been developed based on a 1,3-dipolar cycloaddition of azomethine ylides, generated from isatin and sarcosine or formaldehyde and sarcosine, to adamantine-containing electron-deficient alkenes. Several molecules have demonstrated a considerable cytotoxicity against and A549, HEK293T, MCF7 and VA13 cancer cell lines. The possible mechanism of anticancer activity of synthesised compounds based on literature data may be the inhibition of p53/MDM2 interaction, however, we did not observe significant p53 activation using a reporter construction in A549 cell line in a relevant concentration range.

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 Pharmacological Evaluation of the Anticancer Activity of Extracts and Fractions of Lannea barteri Oliv. (Anacardiaceae) on Adherent Human Cancer Cell Lines

Molecules ◽  
2020 ◽  
Vol 25 (4) ◽  
pp. 849 ◽  
Author(s):  
Florence N. Mbaoji ◽  
Steven Behnisch-Cornwell ◽  
Adaobi C. Ezike ◽  
Chukwuemeka S. Nworu ◽  
Patrick J. Bednarski
Keyword(s):  
Anticancer Activity ◽  
Cell Lines ◽  
Cancer Cell ◽  
Anticancer Agents ◽  
Human Cancer ◽  
Stem Bark ◽  
Cancer Cell Lines ◽  
Human Carcinoma ◽  
Human Cancer Cell Lines ◽  
Western Africa

In western Africa ethnomedicine, Lannea barteri Oliv. (Anacardiaceae) is believed to have activity against gastrointestinal, neurological and endocrine diseases. Previous studies on this plant have revealed antimicrobial, anticholinestrase, anticonvulsant, antioxidant and anti-inflammatory activities. However, the anticancer potential of L. barteri has not been studied to date. The aim of this study was to evaluate the anticancer potential of hot and cold extracts and silica gel column chromatographic fractions of L. barteri leaf and stem bark. The extracts and fractions were tested for anticancer activity by using the crystal violet cell proliferation assay on four adherent human carcinoma cell lines—5637 (bladder), KYSE 70 (oesophagus), SiSo (cervical) and HepG2 (hepatic). The inhibitory concentration (IC50) of fractions IH, 1I, 2E and 2F were: 3.75 ± 1.33, 3.88 ± 2.15, 0.53 ± 0.41, and 0.42 ± 0.45 µg/mL against KYSE 70 and 1.04 ± 0.94, 2.69 ± 1.17, 2.38 ± 3.64, 2.17 ± 1.92 µg/mL against SiSo cell lines respectively. Fraction 2E showed weak apoptotic activity at double the IC50 and some sign of cell cycle arrest in the G2/M phase. Thus, phytoconstituents of L. barteri leaf and stem bark can inhibit the proliferation of cancer cell lines indicating the presence of possible anticancer agents in this plant.

Sulfur Containing Acridine Derivatives in Preclinical Studies with Cancer Cell Lines

2018 ◽  
Vol 25 (17) ◽  
pp. 1968-1975 ◽  
Author(s):  
Salem Othman ◽  
Maria Kozurkova
Keyword(s):  
Anticancer Activity ◽  
Cell Lines ◽  
Cancer Cell ◽  
Anticancer Agents ◽  
Cancer Cell Lines ◽  
Research Literature ◽  
Published Data ◽  
Antitumour Agents ◽  
Acridine Derivatives ◽  
Specific Tumor

Background: The possible use of acridines as anticancer agents was first considered in the 1920´s. Since then, a large number of acridine drugs have been tested as antitumour agents, including compounds containing sulphur on the acridine chromophore. In this review, we will discuss recent studies which have investigated the anticancer activity of this class of acridine derivatives. Methods: We present the results both of our own decade-long research and also of existing research literature into the anticancer activity of acridine derivatives containing sulphur. The evidence of specific tumor-cell killing properties displayed by these compounds suggest the potential of using such molecules as anticancer therapeutics. Results: During the last decade, a number of acridine analogs have been developed by modifying the position and the nature of the substituent on the acridine core. In this paper, we published results on the anticancer activity of acridine derivatives containing sulfur (acridine thioureas, acridine thiazolidine/thiazoidinone, and acridine thiosemicarbazones/ thiosemicarbazides). In cancer chemotherapy, the mechanism of the drugs is complex, although the study of the anticancer activity of acridines has yielded exciting results. Conclusion: In this review we have summarized recent literature on the anticancer activity of acridine derivatives containing sulfur. A considerable amount of published data suggests that these compounds exhibit promising anticancer activity against selected cancer cell lines. The obtained results can be helpful in the development of new pharmaceutical agents.

Synthesis of imidazo[2,1-b][1,3,4]thiadiazole–chalcones as apoptosis inducing anticancer agents

MedChemComm ◽  
2014 ◽  
Vol 5 (11) ◽  
pp. 1718-1723 ◽  
Author(s):  
Ahmed Kamal ◽  
Vangala Santhosh Reddy ◽  
Karnewar Santosh ◽  
G. Bharath Kumar ◽  
Anver Basha Shaik ◽  
...  
Keyword(s):  
Cytotoxic Activity ◽  
Anticancer Activity ◽  
Cell Lines ◽  
Cancer Cell ◽  
Anticancer Agents ◽  
Human Cancer ◽  
Cancer Cell Lines ◽  
Human Cancer Cell ◽  
Human Cancer Cell Lines

A library of imidazothiadiazole–chalcone conjugates were synthesised and investigated for their cytotoxic activity against various human cancer cell lines. Some of the tested compounds like 7a, 7b, 11a and 11b exhibited promising anticancer activity.

Synthesis and anticancer activity of thiadiazole containing thiourea, benzothiazole and imidazo[2,1-b][1,3,4]thiadiazole scaffolds

2020 ◽  
Vol 16 ◽  
Author(s):  
Stephen Paul Avvaru ◽  
Malleshappa N. Noolvi ◽  
Uttam A More ◽  
Sudipta Chakraborty ◽  
Ashutosh Dash ◽  
...  
Keyword(s):  
Anticancer Activity ◽  
Cell Line ◽  
Cell Lines ◽  
Cancer Cell ◽  
Antitumor Agents ◽  
Data Bank ◽  
Cancer Cell Lines ◽  
Docking Studies ◽  
Human Leukemia

Background: A great array of nitrogen-containing heterocyclic rings were being extensively explored for their functional versatility in the field of medicine especially in anticancer research. 1,3,4-thiadiazole is one of such heterocyclic ring with promising anticancer activity against several cancer cell lines, inhibiting diverse biological targets. Introduction: The 1,3,4-thiadiazole, when equipped with other heterocyclic scaffolds, has displayed enhanced anticancer properties. The thiourea, benzothiazole, imidazo[2,1,b][1,3,4]-thiadiazoles are such potential scaffolds with promising anticancer activity. Method: A new series of 5-substituted-1,3,4-thiadiazoles linked with phenyl thiourea, benzothiazole and 2,6-disubstituted imidazo[2,1- b][1,3,4]thiadiazole derivatives were synthesized and tested for in-vitro anticancer activity on various cancer cell lines. Results: The National Cancer Institute’s preliminary anticancer screening results showed compounds 4b and 5b having potent antileukemic activity. Compound 4b selectively showed 32 percent lethality on Human Leukemia-60 cell line. The docking studies of the derivatives on aromatase enzyme (Protein Data Bank: 3S7S) have shown reversible interactions at the active site with good docking scores comparable to Letrozole and Exemestane. Further, the selected derivatives were tested for anticancer activity on HeLa cell line based on the molecular docking studies. Conclusion: Compound 4b and 5b showed effective inhibition equivalent to Letrozole. These preliminary biological screening studies have given positive anticancer activity for these new classes of derivatives. An additional research study like the mechanism of action of the anticancer activity of this new class of compounds is necessary. These groundwork studies illuminate a future pathway for research of this class of compounds enabling the discovery of potent antitumor agents.

Green Synthesis of Metal Nanoparticles from Adiantum Frond: Comparative Analysis on Cancer Cell Lines

2020 ◽  
Vol 10 (6) ◽  
pp. 806-816
Author(s):  
Sabiha Zamani ◽  
Danish Idrees ◽  
Babita Jha ◽  
Anal K. Jha
Keyword(s):  
Breast Cancer ◽  
Gold Nanoparticles ◽  
Anticancer Activity ◽  
Cell Line ◽  
Cell Lines ◽  
Cancer Cell ◽  
Mtt Assay ◽  
Cancer Cell Lines ◽  
Ag Nps ◽  
Au Nps

Background:: At the present time, silver and gold nanoparticles are emerging as promising agents for cancer therapy. The anticancer activities of these nanoparticles have been evaluated against numerous human cancer cell lines. Still, few reports were existing against the breast cancer cell lines and most of these studies have mainly used chemically mediated nanoparticles. Objective:: This study reports the in vitro anticancer activity of bioinspired Nanoparticles like, silver and gold against MCF-7 cells (breast cancer cell line) as well as HEK293 cell (human embryonic kidney cell line) by MTT assay. Methods: These metal nanoparticles, Ag-NPs and Au-NPs were biologically synthesized using Adiantum sp. aqueous leaves extract. The Adiantum sp. can reduce HAuCl4 solution to Au-NPs and AgNO3 to Ag-NPs within 30 mins. The formation of NPs was confirmed by characterization techniques such as UV-vis spectrophotometer, SEM and XRD studies. Additionally, the anticancer activity was analysed by cell viability (3(4,5-dimethly-thiazol-2-yl)- 2,5-diphenyl tetrazo-lium bromide assay). Results: The synthesized nanoparticles from Adiantum sp. were characterized by UV-visible spectroscopy. The role of functional groups was analysed using a Fourier Transform Infrared (FTIR) spectrophotometer. The XRD pattern clearly exemplified that the nanoparticles formed in this present synthesis are crystalline in nature. Furthermore, in MTT assay study, both NPs have shown cytotoxicity at different concentrations ranging from 2.5 to 100 μg/ml. The data reveal that the NPs from Adiantum explicitly, inhibits the viability of cancerous cell only and are non-cytotoxic to HEK293 cells in the tested concentration range. Conclusion: The results provide a preliminary guidance that Adiantum mediated silver and gold nanoparticles might be used to treat breast cancer; however, it necessitates clinical studies to ascertain their potential as anticancer agents.

scholarly journals EVALUATION OF IN VITRO CYTOTOXIC AND ANTICANCER ACTIVITY OF HEPATOPROTECTIVE POLYHERBAL FORMULATION IN CELL LINE MODEL

2019 ◽  
pp. 320-325
Author(s):  
JAYACHANDRA KUNCHA ◽  
THIRUGNANASAMBANTHAM P ◽  
KUMARAN S ◽  
NARAYANAN N ◽  
SHARMILA DEVI V
Keyword(s):  
Anticancer Activity ◽  
Cell Lines ◽  
Cancer Cell ◽  
Anticancer Agents ◽  
Kidney Cell ◽  
Normal Liver ◽  
Cancer Cell Lines ◽  
Polyherbal Formulation ◽  
Ic50 Values

Introduction: The use of natural products as anticancer agents has a long history that began with folklore medicine and through the years has been incorporated into traditional and allopathic medicine. Several drugs currently used are derived from medicinal plants. Objective: The main objective of this study is to investigate the cytotoxic potential of hepatoprotective polyherbal formulation in normal and cancer cell lines. Methods: A 3-(4,5-dimethythiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was utilized to screen the cytotoxic activity. Results: The results revealed that the formulation does not induce much mortality in normal liver and kidney cell lines, and LC50 value of liver cell lines was found 1716.355 μg/ml and kidney cell lines 2464.910 μg/ml. The in vitro anticancer activity was performed on liver, colon, and prostate cancer cell lines, and IC50 values are found 2.077, 3.850, and 11.989 μg/ml, respectively, which show excellent anticancer activity. Conclusion: Based on the results obtained, the hepatoprotective polyherbal formulation is safe for normal cells and cytotoxic for cancer cells. Further, identification and quantification of phytoconstituents responsible for the activity are in progress.

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