scholarly journals Synthesis and Biological Screening of New Thiadiazolopyrimidine-based Polycyclic Compounds

2021 ◽  
Author(s):  
Alaa M. Alqahtani
Keyword(s):  
Cytotoxic Activity ◽  
Fibroblast Cell ◽  
Docking Studies ◽  
Normal Fibroblast ◽  
Polycyclic Compounds ◽  
Gram Positive Bacteria ◽  
Standard Normal ◽  
Structural Activity Relationship ◽  
Cyclic Compounds ◽  
Mcf 7

Abstract New tri- and tetra-cyclic compounds based on the thiadiazolopyrimidine ring system were prepared and their antimicrobial activity were estimated. The achieved results evidenced that pyrano-thiadiazolopyrimidine compounds 8a-b and 9a-b have substantial efficiencies toward the two strains of Gram-positive bacteria (S. aureus and B. cereus). While tetracyclic derivatives pyrazolopyrimido-thiadiazolopyrimidine derivatives 16a-b and 17a-b displayed prominent efficiencies toward the two strains of Gram-negative bacteria (E. coli and P. aeruginosa). In addition, compounds 8a-b and 9a-b presented good efficacy toward C. albicans. The activity of antiquorum-sensing (anti-QS) inhibition of the new synthesized thiadiazolopyrimidine-based compounds was tested toward C. violaceum, where derivatives 16a-b, 17a-b, 8b and 9a displayed satisfactory activity. Cytotoxic activity of the same derivatives was screened toward various cancer cell lines (MCF-7, PC3, Hep-2 and HepG2) and standard normal fibroblast cell (WI38) by utilizing the MTT assay. The pyrazolopyrimido-thiadiazolopyrimidine derivatives 16a, 16b, 17a and 17b recorded potent cytotoxic efficacy against MCF-7 cells with IC50 values ranging from 5.69 to 9.36 µM. Also, the endorsed structural activity relationship (SAR) for the inspected thiadiazolopyrimidine derivatives provided an awareness concerning the chemical structure connected to anticancer efficiency. In silico docking studies were implemented toward silence hormone signaling in breast (PDB Code-5NQR). The results are consistent and supportive to the cytotoxic activity.

scholarly journals Synthesis and biological screening of new thiadiazolopyrimidine-based polycyclic compounds

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Alaa M. Alqahtani
Keyword(s):  
Cytotoxic Activity ◽  
Docking Studies ◽  
Normal Fibroblast ◽  
Polycyclic Compounds ◽  
In Silico Docking ◽  
Gram Positive Bacteria ◽  
Standard Normal ◽  
Structural Activity Relationship ◽  
Cyclic Compounds ◽  
Mcf 7

AbstractNovel tri-and tetra-cyclic compounds based on the thiadiazolopyrimidine ring system were synthesized, and their antimicrobial activity was estimated. The obtained results evidenced the substantial efficiencies of pyrano-thiadiazolopyrimidine compounds 8a–b and 9a–b toward the two strains of gram-positive bacteria (S. aureus and B. cereus). Besides, tetracyclic pyrazolopyrimido-thiadiazolopyrimidine derivatives 16a–b and 17a–b displayed prominent efficiencies toward the two strains of gram-negative bacteria (E. coli and P. aeruginosa). In addition, compounds 8a–b and 9a–b displayed good efficacy toward C. albicans. The activity of antiquorum sensing (anti-QS) inhibition of the newly synthesized thiadiazolopyrimidine-based compounds toward C. violaceum was tested, suggesting satisfactory activity for derivatives 16a–b, 17a–b, 8b, and 9a. The cytotoxic activity of these derivatives was screened toward various cancer cell lines (MCF-7, PC3, Hep-2, and HepG2) and standard normal fibroblast cells (WI38) by utilizing the MTT assay. The pyrazolopyrimido-thiadiazolopyrimidine derivatives 16a, 16b17a, and 17b showed potent cytotoxic efficacy against the MCF-7 cells with the IC50 values ranging from 5.69 to 9.36 µM. Also, the endorsed structural activity relationship (SAR) of the inspected thiadiazolopyrimidine derivatives provided a correlation between the chemical structure and anticancer efficiency. The in silico docking studies were implemented for silencing the hormonal signaling in the breast (PDB Code-5NQR). The results were found to be consistent with the cytotoxic activity.

The in vitro therapeutic activity of betulinic acid nanocomposite on breast cancer cells (MCF-7) and normal fibroblast cell (3T3)

2014 ◽  
Vol 49 (23) ◽  
pp. 8171-8182 ◽  
Author(s):  
Samer Hasan Hussein-Al-Ali ◽  
Palanisamy Arulselvan ◽  
Sharida Fakurazi ◽  
Mohd Zobir Hussein
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Betulinic Acid ◽  
Breast Cancer Cells ◽  
Fibroblast Cell ◽  
Normal Fibroblast ◽  
Therapeutic Activity ◽  
Mcf 7

scholarly journals Imidazole and carbazole derivatives as potential anticancer agents: molecular docking studies and cytotoxic activity evaluation

2020 ◽  
Vol 34 (2) ◽  
pp. 377-384
Author(s):  
B. Taheri ◽  
M. Taghavi ◽  
M. Zarei ◽  
N. Chamkouri ◽  
A. Mojaddami
Keyword(s):  
Molecular Docking ◽  
Cytotoxic Activity ◽  
Cell Lines ◽  
Biological Activities ◽  
Docking Studies ◽  
Carbazole Derivatives ◽  
Ic50 Values ◽  
Docking Energy ◽  
Ht 29 ◽  
Mcf 7

Carbazoles and imidazole represent two important classes of heterocycles which exhibit diverse biological activities such as antitumor properties. In this study, imidazole (C1-C3) and carbazole (C4 and C5) derivatives were evaluated for their cytotoxic activity against three human cancer cell lines namely, MCF7 (human breast cancer), HT29 (human colon cancer), and HeLa (human cervical cancer). Carbazole derivatives (C4 and C5) with IC50 < 10 µM showed greater cytotoxic effect than imidazole derivatives (C1-C3). Furthermore, all compounds exhibited better anticancer activity against MCF-7 than other two cell lines (HT-29, HeLa) and compound C4 was the most potent compound with the IC50 values of 2.5, 5.4 and 4.0 µM, against MCF-7, Hela and HT-29 cell lines, respectively. Physicochemical properties of compounds were calculated and their correlation with the IC50 values on MCF-7 cell line investigated. Surface area and polarizability of compounds showed good correlation by R2 = 0.8396 and R2 = 0.834, respectively. Docking studies of these compounds were also performed on the DNA as proposed target to comprehend their binding interactions and binding energies. The docking energy of compounds ranged from - 11.32 to -13.48 kcal/mol. Compound C3 with energy of -13.48 kcal/mol had the highest docking energy. Docking results indicated that these compounds (C1-C5) had strong affinity in binding to the DNA.                     KEY WORDS: Imidazole, Carbazole, Molecular docking, Cancer, MTT assay   Bull. Chem. Soc. Ethiop. 2020, 34(2), 377-384 DOI: https://dx.doi.org/10.4314/bcse.v34i2.14

Cytotoxic activity and anti-cancer potential of Ontario grown onion extracts against breast cancer cell lines

2018 ◽  
Vol 8 (3) ◽  
pp. 159 ◽  
Author(s):  
Meghan Fragis ◽  
Abdulmonem I. Murayyan ◽  
Suresh Neethirajan
Keyword(s):  
Breast Cancer ◽  
Cytotoxic Activity ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Cancer Cell Lines ◽  
Breast Cancer Cell Lines ◽  
Cytotoxic Activities ◽  
Cancer Line ◽  
Mcf 7

Background: Breast cancer is the most commonly diagnosed cancer and the second leading cause of cancer deaths among Canadian women. Cancer management through changes in lifestyle, such as increased intake of foods rich in dietary flavonoids, have been shown to decrease the risk associated with breast, liver, colorectal, and upper-digestive cancers in epidemiologic studies. Onions are high in flavonoid content and one of the most common vegetables. Additionally, onions are used in most Canadian cuisines.Methods: We investigated the effect of five prominent Ontario grown onion (Stanley, Ruby Ring, LaSalle, Fortress, and Safrane) extracts on two subtypes of breast cancer cell lines: a triple negative breast cancer line MDA-MB-231 and an ER+ breast cancer line MCF-7.Results: These onion extracts elicited strong anti-proliferative, anti-migratory, and cytotoxic activities on both the cancer cell lines. Flavonoids present in these onion extracts induced apoptosis, cell cycle arrest in the G2/M phase, and a reduction in mitochondrial membrane potential at dose-dependent concentrations. Onion extracts were more effective against MDA-MB-231 compared to the MCF-7 cell line. Conclusion: In this study, we investigated the extracts synthesized from Ontario-grown onion varieties in inducing anti-migratory, cytostatic, and cytotoxic activities in two sub-types of human breast cancer cell lines. Anti-tumor activity of these extracts depends upon the varietal and can be formulated into nutraceuticals and functional foods for the wellbeing of cancer patients. Overall, the results suggest that onion extracts are a good source of flavonoids with anti-cancerous properties.Keywords: onion extracts; flavonoids; anti-proliferative; breast cancer; cytotoxic activity

Synthesis and Anticancer Activity of New Hydrazide-hydrazones and Their Pd(II) Complexes

2019 ◽  
Vol 16 (5) ◽  
pp. 522-532 ◽  
Author(s):  
Bedia Kocyigit-Kaymakcioglu ◽  
Senem Sinem Yazici ◽  
Fatih Tok ◽  
Miriş Dikmen ◽  
Selin Engür ◽  
...  
Keyword(s):  
Cytotoxic Activity ◽  
Anticancer Activity ◽  
Cell Line ◽  
Cancer Cell ◽  
Cytotoxic Effect ◽  
A549 Cells ◽  
Cancer Cell Line ◽  
Fibroblast Cell ◽  
Reference Drug ◽  
A549 Cancer Cell Line

Background: Hydrazones, one of the important classes of organic molecules, are pharmaceutical agents comprising –CO-NH-N=CH- group in the structure therefore and exhibiting significant biological activity. Methods: 5-Chloro-N’-[(substituted)methylidene] pyrazine-2-carbohydrazide (3a-g) and their Pd(II) complexes (4a-h) were synthesized and investigated in vitro anticancer activity on A549, Caco2 cancer and normal 3T3 fibroblast cell lines, using the MTT assay. Results: Anticancer activity screening results revealed that some compounds showed remarkable cytotoxic effect. Among them, 5-chloro-N'-[(4-hydroxyphenyl)methylidene] pyrazine-2-carbohydrazide (3c) displayed higher cytotoxic activity against A549 cancer cell line than the reference drug cisplatin. Conclusion: Compound 3c showed high cytotoxic activity against A549 cancer cell line but it showed low cytotoxic effect against normal 3T3 fibroblast cell line. Antiproliferative and antimetastatic effects of 3c were determined by the real-time monitoring of cell proliferative system (RTCA DP). The cell proliferation, metastatic and invasive activities of A549 cells were decreased due to increased concentration of 3c.

Insilico studies, synthesis and antitubercular activity of some novel quinoline – azitidinone derivatives

2020 ◽  
Vol 16 ◽  
Author(s):  
Trupti. S. Chitre ◽  
Kalyani. D. Asgaonkar ◽  
Amrut B. Vikhe ◽  
Shital M Patil ◽  
Dinesh. R. Garud ◽  
...  
Keyword(s):  
Combinatorial Library ◽  
3D Qsar ◽  
Antitubercular Activity ◽  
Structural Features ◽  
Docking Studies ◽  
Quinoline Derivatives ◽  
Qsar Models ◽  
Molecular Modeling Studies ◽  
Lead Generation ◽  
Mcf 7

Background: Diarylquinolines like Bedaquiline have shown promising antitubercular activity by their action of Mycobacterial ATPase. Objective: The structural features necessary for good antitubercular activity for a series of quinoline derivatives were explored through computational chemistry tools like QSAR and combinatorial library generation. In the current study, 3-Chloro-4-(2-mercaptoquinoline-3-yl)-1-substitutedphenylazitidin-2-one derivatives have been designed and synthesized based on molecular modeling studies as anti-tubercular agents. Method: 2D and 3DQSAR analysis was used to designed compounds having quinoline scaffold. The synthesized compounds were evaluated against active and dormant strains of Mycobacterium tuberculosis (MTB) H37 Ra and Mycobacterium bovis BCG. The compounds were also tested for cytotoxicity against MCF-7, A549 and Panc-1 cell lines using MTT assay. Binding affinity of designed compounds was gauged by molecular docking studies. Results: Statistically significant QSAR models generated by SA-MLR method for 2D QSAR exhibited r2 = 0.852, q2 = 0.811and whereas 3D QSAR with SA-kNN showed q2 = 0.77. The synthesized compounds exhibited MIC in the range of 1.38-14.59(µg/ml) .These compounds showed some crucial interaction with MTB Atpase. Conclusion: The present study has shown some promising results which can be further explored for lead generation.

New Ferrocene Compounds as Selective Cyclooxygenase (COX-2) Inhibitors: Design, Synthesis, Cytotoxicity and Enzyme-inhibitory Activity

2018 ◽  
Vol 18 (2) ◽  
pp. 295-301 ◽  
Author(s):  
Shabnam Farzaneh ◽  
Elnaz Zeinalzadeh ◽  
Bahram Daraei ◽  
Soraya Shahhosseini ◽  
Afshin Zarghi
Keyword(s):  
Cell Lines ◽  
Inhibitory Activity ◽  
Fibroblast Cell ◽  
Breast Cancer Cell Lines ◽  
Ferrocene Derivatives ◽  
Cox 2 ◽  
Cytotoxicity Effects ◽  
Cox 2 Inhibitors ◽  
Mcf 7

Background: Due to the astonishing properties of ferrocene and its derivatives, it has a broad application in diverse areas. Numerous ferrocene derivatives demonstrated anti-proliferative activity. Also COX-2, as a key isoenzyme for production of prostaglandins, is frequently overexpressed in various cancers. It is now recognized that COX-2 over expression promotes tumorigenic functions which can be suppressed by COX-2 inhibitors, a phenomenon useful for the preventing of tumor progression. The combination of COX-2 inhibitors with other anti-cancer or cancer prevention drugs may reduce their side effects in future cancer prevention and treatment. Objective: Owing to high anticancer potential of ferrocene derivatives and considerable COX-2 inhibitory and cytotoxicity effects of our previously synthesized chalcones, we decided to incorporate the ferrocenyl moiety into appropriate COX-2 inhibitor chalcone based scaffold, to evaluate COX-2 inhibitory activity as well as anticancer activities. Methods: Chalcones were synthesized via clasien-schmidt condensation of methylsulfonyl aldehyde and acetyl ferrocene. Further different amines with solvent free and ultra sound condition were reacted with chalcones to have different 1-ferrocenyl-3-amino carbonyl compounds. Docking study was carried out with Auto Dock vina software. All the newly-synthesized compounds were evaluated for their cyclooxygenase-2 (COX-2) inhibitory activity using chemiluminescent enzyme assays as well as cytotoxicity activity against MCF-7 and T47D and fibroblast cell lines by MTT assay. Results: In vitro COX-1/COX-2 inhibition studies demonstrated that all compounds were selective inhibitors of the COX-2 isozyme with IC50 values in the highly potent 0.05-0.12 µM range, and COX-2 selectivity indexes (SI) in the 148.3-313.7 range. These results indicated that either potency or selectivity of COX-2 inhibitory activity was affected by the nature and size of the substituents on C-3 of propane-1-one. Also anti-proliferative and toxicity activities of synthesized compounds against breast cancer cell lines MCF-7 and T47D and fibroblast cell lines showed that the synthesized compounds had mild to moderate cytotoxicity against MCT7 and T47D breast cancer cell lines at 10 µM concentration. In vitro COX-1/COX-2 inhibition studies and anticancer activity against MCF-7, identified 1-ferrocenyl-3-(4-methylsulfonylphenyl) propen-1-one as a potent compound (IC50 COX-2 = 0.05 µM, MCF-7: % inhibition (at concentration of 10 µM) = 32.7%), and also 1-ferrocenyl-3- (propan-1-amine)-3-(4-methylsulfonylphenyl) propan-1-one showed the most selectivity on COX-2 inhibition (selectivity index= 313.7). Conclusion: A novel group of ferrocene compounds, possessing a methyl sulfonyl COX-2 pharmacophore were synthesized to investigate the effect of different substituents on selectivity and potency of COX-2 inhibitory activity and their cytotoxicity effects. This study indicates that 1-ferrocenyl-3-amino carbonyl compounds having ferrocene motif and methyl sulfonyl COX-2 pharmacophore is a suitable scaffold to design COX-2 inhibitors and anti-cancer agents.

Evaluation of Cytotoxic and Tyrosinase Inhibitory Activities of 2-phenoxy(thiomethyl) pyridotriazolopyrimidines: In Vitro and Molecular Docking Studies

2020 ◽  
Vol 20 (14) ◽  
pp. 1714-1721
Author(s):  
Hatem A. Abuelizz ◽  
El Hassane Anouar ◽  
Mohamed Marzouk ◽  
Mizaton H. Hasan ◽  
Siti R. Saleh ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Kojic Acid ◽  
Docking Studies ◽  
Breast Adenocarcinoma ◽  
Amino Acid Residues ◽  
New Class ◽  
Structure Activity ◽  
Tyrosinase Inhibitors ◽  
Mcf 7

Background: The use of tyrosinase has confirmed to be the best means of recognizing safe, effective, and potent tyrosinase inhibitors for whitening skin. Twenty-four 2-phenoxy(thiomethyl)pyridotriazolopyrimidines were synthesized and characterized in our previous studies. Objective: The present work aimed to evaluate their cytotoxicity against HepG2 (hepatocellular carcinoma), A549 (pulmonary adenocarcinoma), MCF-7 (breast adenocarcinoma) and WRL 68 (embryonic liver) cell lines. Methods: MTT assay was employed to investigate the cytotoxicity, and a tyrosinase inhibitor screening kit was used to evaluate the Tyrosinase (TYR) inhibitory activity of the targets. Results: The tested compounds exhibited no considerable cytotoxicity, and nine of them were selected for a tyrosinase inhibitory test. Compounds 2b, 2m, and 5a showed good inhibitory percentages against TYR compared to that of kojic acid (reference substance). Molecular docking was performed to rationalize the Structure-Activity Relationship (SAR) of the target pyridotriazolopyrimidines and analyze the binding between the docked-selected compounds and the amino acid residues in the active site of tyrosinase. Conclusion: The target pyridotriazolopyrimidines were identified as a new class of tyrosinase inhibitors.

Design, Synthesis and Biological Evaluation of Novel Urea and Thiourea Bearing thieno[3,2-d]-pyrimidines as PI3 Kinase Inhibitors

2018 ◽  
Vol 18 (6) ◽  
pp. 891-902 ◽  
Author(s):  
Srinu Bodige ◽  
Parameshwar Ravula ◽  
Kali Charan Gulipalli ◽  
Srinivas Endoori ◽  
J.N. Narendra Sharath Chandra ◽  
...  
Keyword(s):  
Anticancer Activity ◽  
Cell Lines ◽  
Inhibitory Activity ◽  
Intracellular Signaling ◽  
Research Work ◽  
Docking Studies ◽  
Biological Evaluation ◽  
Intracellular Enzyme ◽  
Ht 29 ◽  
Mcf 7

Background: Phosphatidylinositol-3-kinase α (PI3Kα) is a ubiquitous intracellular enzyme, mainly involved in intracellular signaling pathways, promotes cellular growth, proliferation, and differentiation. Therefore, inhibition of PI3K can be a hotspot in molecular targeted therapy for the treatment of cancer. Methods: The present research work involves molecular docking studies performed to screen derivatives of urea and thiourea bearing thieno [3,2-d]-pyrimidines against the active site of PI3K enzyme using MOE.2008.10. The designed structures (6a-f) and (7a-j) were synthesized by the facile synthetic methods and evaluated for their anticancer activity against HT-29 and MCF-7 cell lines and inhibitory activity against PI3Kα enzyme. Results: Among the tested compounds, 4-(4-(2-(3-(pyrimidin-2-yl)thioureido)ethyl)piperazin-1-yl)thieno[3,2- d]pyrimidine-6-carboxamide (7f) showed the highest anticancer activity against HT-29 and MCF-7 cell lines with IC50 values of 2.18 µM and 4.25 µM, respectively. Further, the same compound also exhibited potent PI3Kα inhibitory activity with IC50 value of 1.26 µM. Conclusion: Docking studies supported the initial pharmacophoric hypothesis and suggested a mode of interaction at the active binding site of PI3Kα, demonstrating that the target compounds were potential inhibitory agents for cancer therapy.

Cytotoxic Constituents from the Bark of Erythrina poeppigiana Against the MCF-7 Breast Cancer Cell Lines

2020 ◽  
Vol 10 (3) ◽  
pp. 257-261
Author(s):  
Tati Herlina ◽  
Merlin ◽  
Mohd. Azlan ◽  
Unang Supratman
Keyword(s):  
Breast Cancer ◽  
Cytotoxic Activity ◽  
Chemical Structure ◽  
Breast Cancer Cell Lines ◽  
Erythrina Poeppigiana ◽  
Structure Activity ◽  
Cancer Line ◽  
Cytotoxic Compounds ◽  
Ic50 Values ◽  
Mcf 7

Background: Erythrina poeppigiana (Leguminosae) is a high-growing plant with an orange flower that is widely distributed in tropical and subtropical countries. This particular plant is widely used in traditional medicine for gynecological complications and the treatment of various diseases. There exists no previous information regarding cytotoxic compounds from this plant. Objective: This research is to isolate cytotoxic compounds from E. poeppigiana. Methods: The isolation step was carried out using a combination of chromatographic techniques to obtain isolated three compounds (1, 2, and 3). Results: The chemical structure of isolated compounds was elucidated by spectroscopic methods and identified as β-erythroidine (1), 8-oxo-β-erythroidine (2), and 8-oxo-α-erythroidine (3). Compounds (1-3) showed cytotoxic activity against MCF-7 breast cancer line with IC50 values of 36.8, 60.8 and 875.4 μM, respectively. Conclusion: Three compounds have been successfully isolated from Erythrina poeppigiana (Leguminosae), showing cytotoxic properties against MCF-7 breast cancer line. Structure-activity relationship studies showed that the presence of enone moiety on compound 1 can reduce its cytotoxic activity towards MCF-7 breast cancer line.

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