Design, Synthesis, and Anticancer Screening for Repurposed Pyrazolo[3,4-d]pyrimidine Derivatives on Four Mammalian Cancer Cell Lines

The present study reports the synthesis of new purine bioisosteres comprising a pyrazolo[3,4-d]pyrimidine scaffold linked to mono-, di-, and trimethoxy benzylidene moieties through hydrazine linkages. First, in silico docking experiments of the synthesized compounds against Bax, Bcl-2, Caspase-3, Ki67, p21, and p53 were performed in a trial to rationalize the observed cytotoxic activity for the tested compounds. The anticancer activity of these compounds was evaluated in vitro against Caco-2, A549, HT1080, and Hela cell lines. Results revealed that two (5 and 7) of the three synthesized compounds (5, 6, and 7) showed high cytotoxic activity against all tested cell lines with IC50 values in the micro molar concentration. Our in vitro results show that there is no significant apoptotic effect for the treatment with the experimental compounds on the viability of cells against A549 cells. Ki67 expression was found to decrease significantly following the treatment of cells with the most promising candidate: drug 7. The overall results indicate that these pyrazolopyrimidine derivatives possess anticancer activity at varying doses. The suggested mechanism of action involves the inhibition of the proliferation of cancer cells.

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In-vitro Cytotoxicity and In-silico Insights of the Multi-target Anticancer Candidates from Haplophyllum tuberculatum

Borneo Journal of Pharmacy ◽

10.33084/bjop.v4i3.1955 ◽

2021 ◽

Vol 4 (3) ◽

pp. 192-201

Author(s):

Mosab Yahya Al-Nour ◽

Ahmed H Arbab ◽

Mohammad Khalid Parvez ◽

Arwa Y Mohamed ◽

Mohammed S Al-Dosari

Keyword(s):

Hela Cell ◽

Anticancer Activity ◽

Cell Lines ◽

In Vitro Cytotoxicity ◽

Binding Modes ◽

Web Servers ◽

Hela Cell Lines ◽

Ic50 Values ◽

Haplophyllum Tuberculatum

This study aimed to investigate the anticancer activity of Haplophyllum tuberculatum(Forsk.) aerial parts ethanol extract and fractions and reveal the potential anticancer targets, binding modes, pharmacokinetics, and toxicity properties of its phytoconstituents. MTT assay was used to investigate the anticancer activity. TargetNet, ChemProt version 2.0, and CLC-Pred web servers were used for virtual screening, and Cresset Flare software was used for molecular docking with the 26 predicted targets. Moreover, pkCSM, swiss ADME, and eMolTox web servers were used to predict pharmacokinetics and safety. Ethanolic extracts of H. tuberculatum on HepG2 and HeLa cell lines showed promising activities with IC50 values 54.12 and 48.1 µg/mL, respectively. Further, ethyl acetate fraction showed the highest cytotoxicity on HepG2 and HeLa cell lines with IC50 values 41.7 and 52.31 µg/mL. Of 70 compounds screened virtually, polygamain, justicidin A, justicidin B, haplotubine, kusunokinin, and flindersine were predicted as safe anticancer drugs candidates. They showed the highest binding scores with targets involved in cell growth, proliferation, survival, migration, tumor suppression, induction of apoptosis, metastasis, and drug resistance. Our findings revealed the potency of H. tuberculatum as a source of anticancer candidates that further studies should support.

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EVALUATION OF IN VITRO CYTOTOXIC EFFECT OF VIOLACEIN PRODUCED BY NOVEL ISOLATE CHROMOBACTERIUM VACCINII CV5 AGAINST THE CERVICAL AND LUNG CANCER CELL

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2017.v10i10.20456 ◽

2017 ◽

Vol 10 (10) ◽

pp. 227 ◽

Cited By ~ 1

Author(s):

Vishnu T Santhosh ◽

Palaniswamy Muthusamy

Keyword(s):

Lung Cancer ◽

Anticancer Activity ◽

Cell Lines ◽

Cancer Cell ◽

A549 Cells ◽

Dependent Manner ◽

Concentration Dependent Manner ◽

Cytotoxicity Activity ◽

Ic50 Values

Objectives: This study investigates the in vitro anticancer activity of the violacein extracted from the Chromobacterium vaccinii CV5.Methods: Natural colorants or dyes derived from flora to fauna are believed to be safe because of nontoxic, noncarcinogenic, and biodegradable in nature. There are a number of natural pigments, but only a few are available in sufficient quantities for industrial production. The cytotoxicity activity of pigment was assessed against the cervical (HeLa) and lung cancer (A549) cell lines using the MTT assay and there by potential cytotoxic activity exhibited by the pigment was identified.Results: The result of the pigment shows potent anticancer activity on the two cancer cell lines tested in a concentration dependent manner. The potent anticancer activity was observed with the pigment with IC50 values of 26 μg/mL on HeLa and 31 μg/mL on A549 cells, respectively.Conclusion: The study is pioneering report for determining the better in vitro anticancer activity of violacein from the novel isolate C. vaccinii CV5.

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Design, Synthesis and in vitro Anticancer Evaluation of New 2H-benzo[b][1,4]thiazin-3(4H)-one Based 1,2,3-Triazoles

Asian Journal of Chemistry ◽

10.14233/ajchem.2019.22223 ◽

2019 ◽

Vol 31 (11) ◽

pp. 2647-2652 ◽

Cited By ~ 1

Author(s):

O. Rajender ◽

S. Narsimha ◽

N. Vasudeva Reddy

Keyword(s):

Anticancer Activity ◽

Cell Lines ◽

Broad Spectrum ◽

Moderate Activity ◽

Design Synthesis ◽

Triazole Derivatives ◽

Cuaac Reaction ◽

Ic50 Values ◽

Mcf 7

A series of novel 2H-benzo[b][1,4]thiazin-3(4H)-one derived from 1,4-disubstituted 1,2,3-triazole derivatives (4a-j and 5a-j) were synthesized using Cu(I) catalyzed azide alkyne cyclization (CuAAC) reaction of the compounds 2 and 3 with various aromatic azides. The examination of in vitro anticancer activity revealed that the compounds 4d and 5d were found to possess a broad spectrum of anticancer activity against three cell lines MCF-7, HeLa and IMR-32 with IC50 values ranging from 26.28 ± 1.5 to 32.06 ± 0.3 M mL-1, respectively. The remaining compounds have shown good to moderate activity against the tested cell lines.

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Evaluation of Antioxidant, Antimicrobial and Anticancer activity of Thiazole Tagged Isatin Hydrazones

JOURNAL OF PHARMACEUTICAL CHEMISTRY ◽

10.14805/jphchem.2016.art52 ◽

2016 ◽

Vol 3 (2) ◽

pp. 4-9 ◽

Cited By ~ 3

Author(s):

Venkateshwarlu Eggadi ◽

Umasankar Kulandaivelu ◽

Sharvana Bhava Bandaru Sheshagiri ◽

Venkateshwar Rao Jupalli

Keyword(s):

Antioxidant Activity ◽

Hela Cell ◽

Cytotoxic Activity ◽

Anticancer Activity ◽

Cell Lines ◽

Wide Spectrum ◽

Zone Of Inhibition ◽

Hela Cell Lines ◽

Ic50 Values ◽

Isatin Derivatives

Isatin and its derivatives is versatile lead molecule for potential bioactive agents and shows wide spectrum of activities. In this study, we evaluated antioxidant, antimicrobial and cytotoxic activity of isatin-3-[N2-(2-benzalaminothiazol-4-yl)] hydrazone derivatives using well defined models. Antioxidant activity of the isatin derivatives (Va-Vj) was evaluated by using the 1, 1-diphenyl-2-picryl hydrazine radicals scavenging assay. The antimicrobial activity is evaluated by cup plate method and anticancer activity is evaluated by MTT assay against HBL-100 & HeLa cell lines. Compound Vh (R = 5-Cl, R1 = OH & R2 = OCH3) showed good antioxidant activity with the IC50 of 8.09 M. In addition Ve and Vi have showned most active antibacterial activity against Bacillus subtilis, Staphylococcus aureus and Escherichia coli with a Zone of Inhibition (mm) 20, 16, 18 and 14, 12, 15 on respective organism at 100 g/disc. The compound Vi have produced a good antifungal activity against Aspergillus niger and Clostridium vericulata with the zone of inhibition values of 9 and 8 mm respectively. These isatin derivatives also among the test compounds, compound Vd (R = 5-Cl, R1 = OH & R2 = OCH3) and compound Vh (R = 5-Cl, R1 = OH & R2 = OCH3) have shown nearly equal cytotoxic activity with IC50 values of 246.53 mM and 247.29 mM against HBL-100 cell lines and HeLa cell lines respectively. From the results, isatin derivatives showed powerful antioxidant activity, antimicrobial and anticancer activity may be due to the halogens substituted at 5th position of isatin. The standard drugs used were ampicillin, clotrimazole, cisplatin and ascorbic acid for antibacterial, antifungal, anticancer and antioxidant respectively.

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IN VITRO CYTOTOXIC ACTIVITY OF ISOLATED COMPOUNDS FROM VIBURNUM PUNCTATUM BUCH-HAM EX D. DON

International Journal of Current Pharmaceutical Research ◽

10.22159/ijcpr.2017v9i1.16622 ◽

2016 ◽

Vol 9 (1) ◽

pp. 85

Author(s):

A. Renjith Alex ◽

K. Ilango

Keyword(s):

Cytotoxic Activity ◽

Anticancer Activity ◽

Cell Lines ◽

Methanol Extract ◽

Methanolic Extract ◽

Human Colon ◽

Human Colon Cancer ◽

Chloroform Methanol ◽

Human Colon Cancer Cells

Objective: The main aim of the study was to screen the isolated compounds of Viburnum Punctatum for its in vitro anticancer activity and its percentage viability against HCT 15 (Human Colon Cancer Cells) Cell lines.Methods: Pet ether, Chloroform, Methanol and Aqueous extracts was prepared and assayed for the presence of phytochemicals. Two compounds were isolated from the methanol extract of Viburnum Punctatum by column chromatography such as ME1 (Quercetin) and ME2 (Kaemferol-3-glycoside) characterised by UV, IR, MS, 1H NMR and 13C NMR. The above isolated compounds were subjected to in vitro anticancer activity on HCT 15 cell lines was evaluated by Micro culture Tetrazolium (MTT) assay.Results: ME1 showed significant cytotoxic activity than the ME2 on HCT 15 cells with a percentage viability of 54.60 and 67.18 in the concentration of 10µg/ml and 50µg/ml respectively.Conclusion: On the basis of obtained results, ME1 and ME2 isolated from a methanolic extract of Viburnum Punctatum represent a new group of cytotoxic against HCT 15 Cell lines.

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The cytotoxic activity of pine needles ethanolic extract of Pinus merkusii on HeLa cell lines

BIO Web of Conferences ◽

10.1051/bioconf/20213303001 ◽

2021 ◽

Vol 33 ◽

pp. 03001

Author(s):

Annise Proboningrat ◽

Amaq Fadholly ◽

Sri Agus Sudjarwo ◽

Fedik Abdul Rantam ◽

Agung Budianto Achmad

Keyword(s):

Cytotoxic Activity ◽

Cell Lines ◽

Anticancer Agents ◽

Anticancer Agent ◽

Ethanolic Extract ◽

In Vitro Cytotoxicity ◽

Hela Cell Lines ◽

Cytotoxicity Assessment ◽

Pinus Merkusii

Several efforts have been made to discover new anticancer agents based on natural ingredients. Meanwhile, previous studies have shown that different Pine genus species exhibit cytotoxic activity against various types of cancer cells. This plant is rich in phenolic compounds, especially procyanidins, flavonoids, and phenolic acids. Therefore, this study aims to investigate the in vitro cytotoxicity of Pinus merkusii needles extract on HeLa cancer cell lines. The cytotoxicity assessment was measured using MTT assay and expressed as IC50 value. The results showed that the ethanolic extract poses a dose and time-dependent cytotoxic activity with an IC50 value of 542.5 µg/ml at 48 hours of incubation. Based on this result, Pinus merkusii needles’ ethanolic extract has the potential of a novel candidate for an anticancer agent.

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Molecular Docking and In Vitro Anticancer Screening of Synthesized Arylthiazole linked 2H-indol-2-one Derivatives as VEGFR-2 Kinase Inhibitors

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520621666211118102139 ◽

2021 ◽

Vol 21 ◽

Author(s):

Nishtha Shalmali ◽

Sandhya Bawa ◽

Md Rahmat Ali ◽

Sourav Kalra ◽

Raj Kumar ◽

...

Keyword(s):

Flow Cytometry ◽

Anticancer Activity ◽

Cell Lines ◽

Cancer Cell ◽

Active Sites ◽

Colorectal Adenocarcinoma ◽

Kinase Inhibitors ◽

Adenocarcinoma Cells ◽

Ic50 Values

Background: Indoline-2,3-dione comprises a leading course group of heterocycles endowed with appealing biological actions, including anticancer activity. There are significant justifications for exploring the anticancer activity of Schiff base derivatives of isatin as a vast number of reports have documented remarkable antiproliferative action of isatin nucleus against various cancer cell lines. Aims and Objectives: A series of arylthiazole linked 2H-indol-2-one derivatives (5a-t) was designed and synthesized as potential VEGFR-2 kinase inhibitors keeping the essential pharmacophoric features of standard drugs, like sunitinib, sorafenib, nintedanib, etc. They were evaluated for their in vitro anticancer activity. The aim of this study was to investigate and assess the anticancer potential of isatin-containing compounds along with their kinase inhibition activity. Methods: The title compounds were synthesized by reacting substituted isatins with para-substituted arylthiazoles using appropriate reaction conditions. Selected synthesized derivatives went under preliminary screening against a panel of 60 cancer cell lines at NCI, the USA, for single-dose and five dose assays. Molecular docking was performed to explore the binding and interactions with the active sites of the VEGFR-2 receptor (PDB Id: 3VHE). Derivatives 5a, 5b, 5c, 5d, 5g, 5h, and 5m were assessed for in vitro inhibition potency against Human VEGFR-2 using ELISA (Enzyme-Linked Immunosorbent Assay) kit. All the target compounds were determined against human colon cancer cell line SW480 (colorectal adenocarcinoma cells). Cellular apoptosis/necrosis was determined by flow cytometry using annexin V-FITC. DNA content of the cells was analyzed by flow cytometry and the cycle distribution was quantified. Results: Compounds 5a and 5g exhibited noteworthy inhibition during a five-dose assay against a panel of 60 cell lines with MID GI50 values of 1.69 and 1.54 µM, respectively. Also, both the lead compounds 5a and 5g demonstrated promising VEGFR-2 inhibitory activity with IC50 values of 5.43±0.95 and 9.63±1.32 µM, respectively. The aforesaid potent compounds were found effective against SW480 (colorectal adenocarcinoma cells) with IC50 values of 31.44 µM and 106.91 µM, respectively. Compound 5a was found to arrest the cell cycle at the G2/M phase, increasing apoptotic cell death. The docking study also supported VEGFR-2 inhibitory activity as both compounds 5a and 5g displayed promising binding and interactions with the active sites of VEGFR-2 receptor (PDB: 3VHE) with docking scores -9.355 and -7.758, respectively. All the compounds obeyed Lipinski’s rule of five. Conclusion: Indoline-2,3-dione and thiazole have huge potential to be considered a steer combination approach for developing promising kinase inhibitors as cancer therapeutics.

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Design, Synthesis, and Structural Characterization of Novel Diazaphenothiazines with 1,2,3-Triazole Substituents as Promising Antiproliferative Agents

Molecules ◽

10.3390/molecules24234388 ◽

2019 ◽

Vol 24 (23) ◽

pp. 4388 ◽

Cited By ~ 3

Author(s):

Morak-Młodawska ◽

Pluta ◽

Latocha ◽

Jeleń ◽

Kuśmierz

Keyword(s):

Anticancer Activity ◽

Cell Lines ◽

Human Fibroblasts ◽

Human Tumor ◽

Design Synthesis ◽

Human Tumor Cell Lines ◽

Ic50 Values ◽

Normal Human ◽

Low Cytotoxicity

A series of novel 1,2,3-triazole-diazphenothiazine hybrids was designed, synthesized, and evaluated for anticancer activity against four selected human tumor cell lines (SNB-19, Caco-2, A549, and MDA-MB231). The majority of the synthesized compounds exhibited significant potent activity against the investigated cell lines. Among them, compounds 1d and 4c showed excellent broad spectrum anticancer activity, with IC50 values ranging from 0.25 to 4.66 μM and 0.25 to 6.25 μM, respectively. The most promising compound 1d, possessing low cytotoxicity against normal human fibroblasts NHFF, was used for gene expression analysis using reverse transcription–quantitative real-time PCR (RT–qPCR). The expression of H3, TP53, CDKN1A, BCL-2, and BAX genes revealed that these compounds inhibited the proliferation in all cells (H3) and activated mitochondrial events of apoptosis (BAX/BCL-2).

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Design, Synthesis, and Biological Evaluation of Pyridineamide Derivatives Containing a 1,2,3-Triazole Fragment as Type II c-Met Inhibitors

Molecules ◽

10.3390/molecules25010010 ◽

2019 ◽

Vol 25 (1) ◽

pp. 10 ◽

Cited By ~ 1

Author(s):

Hehua Xiong ◽

Jianxin Cheng ◽

Jianqing Zhang ◽

Qian Zhang ◽

Zhen Xiao ◽

...

Keyword(s):

Antitumor Activity ◽

Cell Lines ◽

Inhibitory Activity ◽

Docking Simulation ◽

Binding Mode ◽

Biological Evaluation ◽

Design Synthesis ◽

Ic50 Values ◽

Mcf 7

A series of 4-(pyridin-4-yloxy)benzamide derivatives containing a 1,2,3-triazole fragment were designed, synthesized, and their inhibitory activity against A549, HeLa, and MCF-7 cancer cell lines was evaluated. Most compounds exhibited moderate to potent antitumor activity against the three cell lines. Among them, the promising compound B26 showed stronger inhibitory activity than Golvatinib, with IC50 values of 3.22, 4.33, and 5.82 μM against A549, HeLa, and MCF-7 cell lines, respectively. The structure–activity relationships (SARs) demonstrated that the modification of the terminal benzene ring with a single electron-withdrawing substituent (fluorine atom) and the introduction of a pyridine amide chain with a strong hydrophilic group (morpholine) to the hinge region greatly improved the antitumor activity. Meanwhile, the optimal compound B26 showed potent biological activity in some pharmacological experiments in vitro, such as cell morphology study, dose-dependent test, kinase activity assay, and cell cycle experiment. Finally, the molecular docking simulation was performed to further explore the binding mode of compound B26 with c-Met.

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In VitroCytotoxic Potential of Essential Oils ofEucalyptus benthamiiand Its Related Terpenes on Tumor Cell Lines

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2012/342652 ◽

2012 ◽

Vol 2012 ◽

pp. 1-8 ◽

Cited By ~ 32

Author(s):

Patrícia Mathias Döll-Boscardin ◽

Adilson Sartoratto ◽

Beatriz Helena Lameiro de Noronha Sales Maia ◽

Josiane Padilha de Paula ◽

Tomoe Nakashima ◽

...

Keyword(s):

Tumor Cell ◽

Essential Oils ◽

Cytotoxic Activity ◽

Cell Lines ◽

Cytotoxic Effect ◽

Herbal Remedy ◽

Jurkat Cells ◽

Tumor Cell Lines ◽

Hela Cell Lines

EucalyptusL. is traditionally used for many medicinal purposes. In particular, someEucalyptusspecies have currently shown cytotoxic properties. Local Brazilian communities have used leaves ofE. benthamiias a herbal remedy for various diseases, including cancer. Considering the lack of available data for supporting this cytotoxic effect, the goal of this paper was to study thein vitrocytotoxic potential of the essential oils from young and adult leaves ofE. benthamiiand some related terpenes (α-pinene, terpinen-4-ol, andγ-terpinene) on Jurkat, J774A.1 and HeLa cells lines. Regarding the cytotoxic activity based on MTT assay, the essential oils showed improved results thanα-pinene andγ-terpinene, particularly for Jurkat and HeLa cell lines. Terpinen-4-ol revealed a cytotoxic effect against Jurkat cells similar to that observed for volatile oils. The results of LDH activity indicated that cytotoxic activity of samples against Jurkat cells probably involved cell death by apoptosis. The decrease of cell DNA content was demonstrated due to inhibition of Jurkat cells proliferation by samples as a result of cytotoxicity. In general, the essential oils from young and adult leaves ofE. benthamiipresented cytotoxicity against the investigated tumor cell lines which confirms their antitumor potential.

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