scholarly journals Design and Synthesis of 4-O-Podophyllotoxin Sulfamate Derivatives as Potential Cytotoxic Agents

2021 ◽  
Vol 2021 ◽  
pp. 1-7
Author(s):  
Ammar Bader ◽  
Majdi M. Bkhaitan ◽  
Ashraf N. Abdalla ◽  
Qasem M. A. Abdallah ◽  
Hamed I. Ali ◽  
...  
Keyword(s):  
Sulfonyl Chloride ◽  
Colon Adenocarcinoma ◽  
Biological Evaluation ◽  
Cytotoxic Agents ◽  
Normal Lung ◽  
Dependent Manner ◽  
Mcf7 Cells ◽  
Design And Synthesis ◽  
Apoptotic Effect ◽  
Mrc5 Cell

4-O-Podophyllotoxin sulfamate derivatives were prepared using the natural lignan podophyllotoxin. The prepared compounds were afforded by reacting O-sulfonyl chloride podophyllotoxin with ammonia or aminoaryl/heteroaryl motif. Biological evaluation was performed in human breast cancer (MCF7), ovarian cancer (A2780), colon adenocarcinoma (HT29), and normal lung fibroblast (MRC5) cell lines. Compound 3 exhibited potent inhibitory activity and good selectivity margin. Compounds 2, 3, and 7 exerted apoptotic effect in MCF7 cells in a dose-dependent manner. The cytotoxicity of the verified compounds was inferior to that of podophyllotoxin.

Synthesis, Characterization and Biological Evaluation of Novel Triazolyl - Acridine Derivatives as Cytotoxic Agents

2021 ◽  
pp. 5101-5107
Author(s):  
Mandeep Singh ◽  
D. N Prasad ◽  
Supriya Agnihotri
Keyword(s):  
Cell Line ◽  
Biological Evaluation ◽  
Biologically Active ◽  
Cytotoxic Agents ◽  
Breast Adenocarcinoma ◽  
Dependent Manner ◽  
Adenocarcinoma Cell Line ◽  
Adenocarcinoma Cell ◽  
Ht 29 ◽  
Mcf 7

Acridine and Triazols both are biologically active heterocyclic rings with cytotoxic potential. Triazolyl- acridine adduct attract the attention in the field of medicinal chemistry. Here we synthesized a series of triazolyl- acridine compounds by the appropriate procedures. Structure of all synthesized compounds was confirmed by the various spectroscopic methods e.g. FT-IR, proton NMR and Mass spectrograms. All synthesized triazolyl-acirdines compounds were assayed in-vitro for cytotoxic activity against MCF-7 (human breast adenocarcinoma cell line) and HT-29 (human colon adenocarcinoma cell line) cells by MTT- assay. All target compounds shows increasing activity in dose dependent manner. However MPSP-9 was sensitive against MCF-7 but compound MPSP-1 was most sensitive with minimum inhibitory concentration (IC50 value) against MCF-7 and HT-29 both cell lines.

Biological Evaluation and Molecular Modeling of 3,4-dihydropyrimidine- 2(1H)-one Derivatives as Cytotoxic Agents on Breast Cancer In Vitro

2020 ◽  
Vol 17 (8) ◽  
pp. 983-992
Author(s):  
Hoda Sharifi ◽  
Ahmad Ebadi ◽  
Meysam Soleimani
Keyword(s):  
Molecular Modeling ◽  
Anticancer Agents ◽  
Antitumor Agents ◽  
Biological Evaluation ◽  
Cytotoxic Agents ◽  
Polymerization Process ◽  
Dependent Manner ◽  
Cytotoxic Effects ◽  
Receptor Complexes ◽  
Amide Derivatives

Background: Kinesins and tubulin inhibitors have attracted researchers’ attention as hopeful targets for achieving effective anticancer agents. Dihydropyrimidine-2-ones (DHPMs) inhibit motor proteins Eg5 in the polymerization process of tubulin, also scaffold bearing benzothiazole heterocycle can block tubulin polymerization/depolymerization. Objective: In this study, the cytotoxic effects and molecular modeling of newly synthesized derivatives of DHPM that were designed by the Scaffold-hopping approach were investigated as potential dual-inhibitors of Eg5 and tubulin. Methods: We investigated the cytotoxic effects of DHPMs derivatives by MTT assay and measureing the Caspase 3 activity. Also, molecular modeling studies were performed by AutoDock4 and GROMACS 4.5.6. Results: According to the results, the d2 derivative (IC50 = 68.58 ± 7, SI = 2.57) eliminates MDA-MB- 231 cells in a dose-dependent manner through caspase-dependent and caspase-independent cell death pathways. Molecular docking studies revealed that the d2 compound could interact with both Eg5 and tubulin key residues. MD simulation also demonstrated the stability of the studied ligand-receptor complexes during the 30 ns of the production run. The effectiveness of substitutions at C4 of the DHPM ring was obtained 4-acetoxy-phenyl, 4-methoxyphenyl, and 4-nitrophenyl, respectively. Conclusion: The findings of the present study provide evidence that DHPM C5 amide derivatives bearing benzothiazole ring might be considered as promising lead compounds for the discovery of novel and multi-target antitumor agents.

Paeonol Inhibits Prostate Cancer Cell Invasion and Epithelial-Mesenchymal Transformation by Inactivation of STAT3 Pathway

2020 ◽  
Vol 19 (1) ◽  
pp. 15-20
Author(s):  
Junyi Xiang ◽  
Feng Huang ◽  
Renhua Huang ◽  
Jingzhan Su ◽  
Yulong Liu
Keyword(s):  
Prostate Cancer ◽  
Treatment Options ◽  
Surrogate Marker ◽  
Cytotoxic Agents ◽  
Potential Candidate ◽  
Dependent Manner ◽  
Ablation Therapy ◽  
Androgen Ablation ◽  
Mesenchymal Transformation ◽  
Dose Dependent

Prostate cancer is one of the leading causes of death in men all over the world. Treatment options such as androgen ablation therapy and cytotoxic agents have many undesirable side effects, narrow therapeutic windows, or other limitations. In this research, we have explored the effects of paeonol on prostate cancer and its mechanism of action. Our results have shown that paeonol reduced the viability of prostate cancer cells in a dose-dependent manner. The wound-healing assay, a surrogate marker of tumor metastasis, showed that the relative wound width of 10 µM group was less than that of 50 µM paeonol-treated cells. Besides, the results of the transwell assay also showed that the number of migrated cells was significantly lower after treatment with 50 µM paeonol compared to the 10 µM group. The Western blot results showed that paeonol treatment induced a decrease in the mesenchymal markers (vimentin and N-cadherin), while the epithelial marker (E-cadherin) increased in a dose-dependent manner suggesting that paeonol effectively inhibits the epithelial-mesenchymal transformation in PC3 cells. Furthermore, the expression of STAT3 and p-STAT3 was also decreased after paeonol treatment, which indicated that the STAT3 signaling pathway was inhibited by paeonol. To conclude, the results summarized in this paper suggest that paeonol could be a potential candidate in the treatment of prostate cancer.

Synthesis of Sulfur Containing Colchicine Derivatives and their Biological Evaluation as Cytotoxic Agents

2014 ◽  
Vol 11 (3) ◽  
pp. 279-289 ◽  
Author(s):  
Joanna Kurek ◽  
Wladyslaw Boczon ◽  
Krzysztof Myszkowski ◽  
Marek Murias ◽  
Teresa Borowiak ◽  
...  
Keyword(s):  
Biological Evaluation ◽  
Cytotoxic Agents ◽  
Colchicine Derivatives ◽  
Sulfur Containing

Synthesis and Biological Evaluation of Novel Osthol Derivatives as Potent Cytotoxic Agents

2019 ◽  
Vol 15 (2) ◽  
pp. 138-149
Author(s):  
Saleem Farooq ◽  
Javid A. Banday ◽  
Aashiq Hussain ◽  
Momina Nazir ◽  
Mushtaq A. Qurishi ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Natural Product ◽  
Cancer Therapeutics ◽  
Inhibitory Effect ◽  
Biological Evaluation ◽  
Negative Control ◽  
Normal Breast ◽  
Cytotoxic Agents ◽  
Breast Epithelial Cell ◽  
Exciting Field

Background: Natural product, osthol has been found to have important biological and pharmacological roles particularly having inhibitory effect on multiple types of cancer. Objective: The unmet needs in cancer therapeutics make its derivatization an important and exciting field of research. Keeping this in view, a whole new series of diverse analogues of osthol (1) were synthesized. Method: All the newly synthesized compounds were made through modification in the lactone ring as well as in the side chain of the osthol molecule and were subjected to anti-proliferative screening through 3-(4,5-Dimethylthiazol-yl)-diphenyl tetrazoliumbromide (MTT) against four different human cancers of diverse origins viz. Colon (Colo-205), lung (A549), Leukemia (THP- 1) and breast (MCF-7) including SV40 transformed normal breast epithelial cell (fR-2). Results: Interestingly, among the tested molecules, most of the analogs displayed better antiproliferative activity than the parent Osthol 1. However, among all the tested analogs, compound 28 exhibited the best results against leukemia (THP1) cell line with IC50 of 5µM.Compound 28 induced potent apoptotic effects and G1 phase arrest in leukemia cancer cells (THP1). The population of apoptotic cells increased from 13.8% in negative control to 26.9% at 8μM concentration of 28. Compound 28 also induced a remarkable decrease in mitochondrial membrane potential (ΛΨm) leading to apoptosis of the cancer cells. Conclusion: A novel series of molecules derived from natural product osthol were synthesized, wherein compound 28 was found to be most effective against leukemia and with 10 fold less toxicity against normal cells. The compound induced cancer inhibition mainly through apoptosis and thus has a potential in cancer therapeutics.

Design, Synthesis and Cytotoxicity Evaluation of New 3, 5-Disubstituted-2-Thioxoimidazolidinones

2018 ◽  
Vol 18 (4) ◽  
pp. 573-582 ◽  
Author(s):  
Khaled R.A. Abdellatif ◽  
Mostafa M. Elbadawi ◽  
Mohammed T. Elsaady ◽  
Amer A. Abd El-Hafeez ◽  
Takashi Fujimura ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Line ◽  
Cell Lines ◽  
Cancer Cell ◽  
Topoisomerase I ◽  
Cancer Cell Line ◽  
Cytotoxic Agents ◽  
Dependent Manner ◽  
Human Lung Fibroblast ◽  
Mcf 7

Background: Some 2-thioxoimidazolidinones have been reported as anti-prostate and anti-breast cancer agents through their inhibitory activity on topoisomerase I that is considered as a potential chemotherapeutic target. Objective: A new series of 3,5-disubstituted-2-thioxoimidazolidinone derivatives 10a-f and their S-methyl analogs 11a-f were designed, synthesized and evaluated for cytotoxicity against human prostate cancer cell line (PC-3), human breast cancer cell line (MCF-7) and non-cancerous human lung fibroblast cell line (WI-38). </P><P> Results and Method: While compounds 10a-f showed a broad range of activities against PC-3 and MCF-7 cell lines (IC50 = 34.0 – 186.9 and 24.6 – 147.5 µM respectively), the S-methyl analogs 11a-f showed (IC50 = 22.7 – 198.5 and 16.9 – 188.2 µM respectively) in comparison with 5-fluorouracil (IC50 = 60.7 and 40.7 µM respectively). 11c (IC50 = 22.7 and 29.2 µM) and 11f (IC50 = 28.7 and 16.9 µM) were the most potent among all compounds against both PC-3 and MCF-7 respectively with no cytotoxicity against WI-38. Conclusion: The newly synthesized compounds showed good activity against PC-3 and MCF-7 cell lines in comparison with 5-fluorouracil. Compounds 11c and 11f bound with human topoisomerase I similar to its known inhibitors and significantly inhibited its DNA relaxation activity in a dose dependent manner which may rationalize their molecular mechanism as cytotoxic agents.

Synthesis and Biological Evaluation of Novel Heterocyclic Imines Linked Coumarin- Thiazole Hybrids as Anticancer Agents

2019 ◽  
Vol 19 (4) ◽  
pp. 557-566 ◽  
Author(s):  
Nerella S. Goud ◽  
Mahammad S. Ghouse ◽  
Jatoth Vishnu ◽  
Jakkula Pranay ◽  
Ravi Alvala ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Membrane Potential ◽  
Fluorescence Spectroscopy ◽  
Mitochondrial Membrane Potential ◽  
Mitochondrial Membrane ◽  
Annexin V ◽  
Biological Evaluation ◽  
Dependent Manner ◽  
Dapi Staining ◽  
Dose Dependent

Background: Human Galectin-1, a protein of lectin family showing affinity towards β-galactosides has emerged as a critical regulator of tumor progression and metastasis, by modulating diverse biological events including homotypic cell aggregation, migration, apoptosis, angiogenesis and immune escape. Therefore, galectin-1 inhibitors might represent novel therapeutic agents for cancer. Methods: A new series of heterocyclic imines linked coumarin-thiazole hybrids (6a-6r) was synthesized and evaluated for its cytotoxic potential against a panel of six human cancer cell lines namely, lung (A549), prostate (DU-145), breast (MCF-7 & MDA-MB-231), colon (HCT-15 & HT-29) using MTT assay. Characteristic apoptotic assays like DAPI staining, cell cycle, annexin V and Mitochondrial membrane potential studies were performed for the most active compound. Furthermore, Gal-1 inhibition was confirmed by ELISA and fluorescence spectroscopy. Results: Among all, compound 6g 3-(2-(2-(pyridin-2-ylmethylene) hydrazineyl) thiazol-4-yl)-2H-chromen-2- one exhibited promising growth inhibition against HCT-15 colorectal cancer cells with an IC50 value of 1.28 ± 0.14 µM. The characteristic apoptotic morphological features like chromatin condensation, membrane blebbing and apoptotic body formation were clearly observed with compound 6g on HCT-15 cells using DAPI staining studies. Further, annexin V-FITC/PI assay confirmed effective early apoptosis induction by treatment with compound 6g. Loss of mitochondrial membrane potential and enhanced ROS generation were confirmed with JC-1 and DCFDA staining method, respectively by treatment with compound 6g, suggesting a possible mechanism for inducing apoptosis. Moreover, flow cytometric analysis revealed that compound 6g blocked G0/G1 phase of the cell cycle in a dose-dependent manner. Compound 6g effectively reduced the levels of Gal-1 protein in a dose-dependent manner. The binding constant (Ka) of 6g with Gal-1 was calculated from the intercept value which was observed as 1.9 x 107 M-1 by Fluorescence spectroscopy. Molecular docking studies showed strong interactions of compound 6g with Gal-1 protein. Conclusion: Our studies demonstrate the anticancer potential and Gal-1 inhibition of heterocyclic imines linked coumarin-thiazole hybrids.

Design and synthesis, biological evaluation of bis-(1,2,3- and 1,2,4)-triazole derivatives as potential antimicrobial and antifungal agents

2021 ◽  
Vol 41 ◽  
pp. 128004
Author(s):  
Sampath Bitla ◽  
Akkiraju Anjini Gayatri ◽  
Muralidhar Reddy Puchakayala ◽  
Vijaya Kumar Bhukya ◽  
Jagadeshwar Vannada ◽  
...  
Keyword(s):  
Antifungal Agents ◽  
Biological Evaluation ◽  
Triazole Derivatives ◽  
Design And Synthesis
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