scholarly journals Synthesis, Anticancer Evaluation and Structure-Activity Analysis of Novel (E)- 5-(2-Arylvinyl)-1,3,4-oxadiazol-2-yl)benzenesulfonamides

2020 ◽  
Vol 21 (6) ◽  
pp. 2235
Author(s):  
Krzysztof Szafrański ◽  
Jarosław Sławiński ◽  
Łukasz Tomorowicz ◽  
Anna Kawiak
Keyword(s):  
Anticancer Activity ◽  
Cell Lines ◽  
Human Tumor ◽  
Structure Activity Relationship ◽  
Activity Relationship ◽  
Structure Activity ◽  
Hela Cell Lines ◽  
Hct 116 ◽  
Mcf 7

To learn more about the structure–activity relationships of (E)-3-(5-styryl-1,3,4-oxadiazol-2-yl)benzenesulfonamide derivatives, which in our previous research displayed promising in vitro anticancer activity, we have synthesized a group of novel (E)-5-[(5-(2-arylvinyl)-1,3,4-oxadiazol-2-yl)]-4-chloro-2-R1-benzenesulfonamides 7–36 as well as (E)-4-[5-styryl1,3,4-oxadiazol-2-yl]benzenesulfonamides 47–50 and (E)-2-(2,4-dichlorophenyl)-5-(2-arylvinyl)-1,3,4-oxadiazols 51–55. All target derivatives were evaluated for their anticancer activity on HeLa, HCT-116, and MCF-7 human tumor cell lines. The obtained results were analyzed in order to explain the influence of a structure of the 2-aryl-vinyl substituent and benzenesulfonamide scaffold on the anti-tumor activity. Compound 31, bearing 5-nitrothiophene moiety, exhibited the most potent anticancer activity against the HCT-116, MCF-7, and HeLa cell lines, with IC50 values of 0.5, 4, and 4.5 µM, respectively. Analysis of structure-activity relationship showed significant differences in activity depending on the substituent in position 3 of the benzenesulfonamide ring and indicated as the optimal meta position of the sulfonamide moiety relative to the oxadizole ring. In the next stage, chemometric analysis was performed basing on a set of computed molecular descriptors. Hierarchical cluster analysis was used to examine the internal structure of the obtained data and the quantitative structure–activity relationship (QSAR) analysis with multiple linear regression (MLR) method allowed for finding statistically significant models for predicting activity towards all three cancer cell lines.

Recent Design and Structure-Activity Relationship Studies on Modifications of DHFR Inhibitors as Anticancer Agents

2019 ◽  
Vol 26 ◽  
Author(s):  
Agnieszka Wróbel ◽  
Danuta Drozdowska
Keyword(s):  
Anticancer Activity ◽  
Anticancer Drugs ◽  
Anticancer Agents ◽  
Physicochemical Characterization ◽  
Structure Activity Relationship ◽  
Activity Relationship ◽  
Biological Research ◽  
Structure Activity ◽  
Dhfr Inhibitors

Background: Dihydrofolate reductase (DHFR) has been known for decades as a molecular target for antibacterial, antifungal and anti-malarial treatments. This enzyme is becoming increasingly important in the design of new anticancer drugs, which is confirmed by numerous studies including modelling, synthesis and in vitro biological research. This review aims to present and discuss some remarkable recent advances on the research of new DHFR inhibitors with potential anticancer activity. Methods: The scientific literature of the last decade on the different types of DHFR inhibitors has been searched. The studies on design, synthesis and investigation structure-activity relationship were summarized and divided into several subsections depending on the leading molecule and its structural modification. Various methods of synthesis, potential anticancer activity and possible practical applications as DHFR inhibitors of new chemical compounds were described and discussed. <p> Results: This review presents the current state of knowledge on the modification of known DHFR inhibitors and the structures and searching for over eighty new molecules, designed as potential anticancer drugs. In addition, DHFR inhibitors acting on thymidylate synthase (TS), carbon anhydrase (CA) and even DNA-binding are presented in this paper. <p> Conclusion: Thorough physicochemical characterization and biological investigations it is possible to understand structure-activity relationship of DHFR inhibitors. This will enable even better design and synthesis of active compounds, which would have the expected mechanism of action and the desired activity.

Current status of novel pyridine fused derivatives as anticancer agents: An insight into future perspectives and structure activity relationship (SAR)

2021 ◽  
Vol 21 ◽  
Author(s):  
Ajay Manaithiya ◽  
Ozair Alam ◽  
Vrinda Sharma ◽  
Mohd. Javed Naim ◽  
Shruti Mittal ◽  
...  
Keyword(s):  
Anticancer Activity ◽  
Anticancer Agents ◽  
Heterocyclic Ring ◽  
Structure Activity Relationship ◽  
Activity Relationship ◽  
Current Status ◽  
Normal Tissues ◽  
Structure Activity ◽  
Prevalent Disease

: Cancer is a heterogeneous disease characterized by an abnormal and uncontrolled division of the cells leading to tumors that invade the adjacent normal tissues. After cardiovascular diseases, it is the second most prevalent disease accounting for one in every six deaths worldwide. This alarming rate thus, demands an urgent need to investigate more effective drugs to combat the said disease. Oxygen and nitrogen-based heterocyclic compounds have shown remarkable therapeutic activity towards several diseases, including cancer. In this review, we have attempted to summarize the work done in the last decade (2009-2019), highlighting the anticancer activity of pyrido fused five-membered heterocyclic ring derivatives. Additionally, we have focused on seven heterocyclic pyridine fused rings: Imidazopyridine, Triazolopyridine, Pyrrolopyridine, Pyrazolopyridines, Thienopyridine, and Isoxazolopyridine. A total of forty-nine compounds have been studied based on their in-vitro cytotoxic activity and their structure-activity relationship, underlining the anticancer activity of their various pharmacophores and substituents. This review, therefore, aims to draw the attention of the researchers worldwide towards the enormous scope of development of heterocyclic drug compounds, focussing mainly on pyrido fused five-membered heterocyclic rings as anticancer drugs.

scholarly journals Synthesis, Anticancer Activity, and Preliminary Pharmacokinetic Evaluation of 4,4-Disubstituted Curcuminoid 2,2-bis(Hydroxymethyl)Propionate Derivatives

Molecules ◽  
2020 ◽  
Vol 25 (3) ◽  
pp. 479 ◽  
Author(s):  
Der-Yen Lee ◽  
Yu-Chi Hou ◽  
Jai-Sing Yang ◽  
Hui-Yi Lin ◽  
Tsu-Yuan Chang ◽  
...  
Keyword(s):  
Anticancer Activity ◽  
Functional Groups ◽  
Hydrolysis Product ◽  
Structure Activity Relationship ◽  
Ester Hydrolysis ◽  
Activity Relationship ◽  
Structure Activity ◽  
Hct 116 ◽  
Pharmacokinetic Evaluation

Compound 1 is a curcumin di-O-2,2-bis(hydroxymethyl)propionate that shows significant in vitro and in vivo inhibitory activity against MDA-MB-231 cells with eight to ten-fold higher potency than curcumin. Here, we modified the α-position (C-4 position) of the central 1,3-diketone moiety of 1 with polar or nonpolar functional groups to afford a series of 4,4-disubstituted curcuminoid 2,2-bis(hydroxymethyl)propionate derivatives and evaluated their anticancer activities. A clear structure–activity relationship of compound 1 derivatives focusing on the functional groups at the C-4 position was established based on their anti-proliferative effects against the MDA-MB-231 and HCT-116 cell lines. Compounds 2–6 are 4,4-dimethylated, 4,4-diethylated, 4,4-dibenzylated, 4,4-dipropargylated and 4,4-diallylated compound 1, respectively. Compounds 2m–6m, the ester hydrolysis products of compounds 2–6, respectively, were synthesized and assessed for anticancer activity. Among all compound 1 derivatives, compound 2 emerged as a potential chemotherapeutic agent for colon cancer due to the promising in vivo anti-proliferative activities of 2 (IC50 = 3.10 ± 0.29 μM) and its ester hydrolysis product 2m (IC50 = 2.17 ± 0.16 μM) against HCT-116. The preliminary pharmacokinetic evaluation of 2 implied that 2 and 2m are main contributors to the in vivo efficacy. Compound 2 was further evaluated in an animal study using HCT-116 colon tumor xenograft bearing nude mice. The results revealed a dose-dependent efficacy that led to tumor volume reductions of 27%, 45%, and 60% at 50, 100, and 150 mg/kg doses, respectively. The established structure–activity relationship and pharmacokinetic outcomes of 2 is the guidance for future development of 4,4-disubstituted curcuminoid 2,2-bis(hydroxymethyl)- propionate derivatives as anticancer drug candidates.

scholarly journals CYTOTOXIC AND ANTIOXIDANT ACTIVITIES OF SECONDARY METABOLITES FROM PULICARIA UNDULATA

2016 ◽  
Vol 8 (9) ◽  
pp. 150 ◽  
Author(s):  
Taha A. Hussien ◽  
Sayed A. El-toumy ◽  
Hossam M. Hassan ◽  
Mona H. Hetta
Keyword(s):  
Antioxidant Activity ◽  
Secondary Metabolites ◽  
Antioxidant Activities ◽  
Structure Activity Relationship ◽  
Activity Relationship ◽  
Hep G2 ◽  
Structure Activity ◽  
Dpph Method ◽  
Mcf 7

<p><strong>Objective:</strong><strong> </strong>To evaluate the <em>in vitro</em> cytotoxicity, antioxidant activities and structure-activity relationship of secondary metabolites isolated from <em>Pulicaria undulata</em>.</p><p><strong>Methods: </strong>The methylene chloride-methanol (1:1) extract of the air-dried aerial parts of <em>Pulicaria undulata</em> was fractionated and separated to obtain the isolated compounds by different chromatographic techniques. Structures of the isolated compounds were determined on the basis of the extensive spectroscopic analysis, including 1D and 2D NMR and compared with the literature data. The crude extract and the isolated compounds were evaluated for <em>in vitro</em> antioxidant activity using the 2,2 diphenyl dipicryl hydrazine (DPPH) method and cytotoxic assay using human breast cancer (MCF-7) and hepatoma (Hep G2) cell line.</p><p><strong>Results: </strong>Nine secondary metabolites were isolated from <em>Pulicaria undulata</em> in this study. Of which two terpenoidal compounds; 8-epi-ivalbin and 11β, 13-dihydro-4H-xanthalongin 4-<em>O</em>-β-D-glucopyranoside firstly isolated from the genus <em>pulicaria</em> and three flavonoids; eupatolitin, 6-methoxykaempferol, and patulitrin firstly isolated from <em>P. undulata</em>. 6-methoxykaempferol (IC<sub>50</sub> 2.3 µg/ml) showed the most potent antioxidant activity. The highest cytotoxic effect against MCF-7 and Hep G2 cells was obtained with eupatolitin (IC<sub>50</sub> 27.6 and 23.5 µg/ml) respectively. The structure-activity relationship was also examined and the findings presented here showed that 3, 5, 7, 4' and 3, 5, 4', 5'-hydroxy flavonoids were potent antioxidant and has cytotoxic activity.</p><p><strong>Conclusion: </strong><em>Pulicaria undulata</em> is a promising medicinal plant, and our study tends to support the therapeutic value of this plant as antioxidant drug and in the treatment of cancer.</p>

Antiproliferative Activity of 8-methoxy Ciprofloxacin-Hydrozone/Acylhydrazone Scaffolds

2020 ◽  
Vol 20 (21) ◽  
pp. 1911-1915
Author(s):  
Li-Ping Wang ◽  
Zhi Xu ◽  
Gui-Ying Deng ◽  
Sha-Li Xu
Keyword(s):  
Anticancer Activity ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Structure Activity Relationship ◽  
Activity Relationship ◽  
Prostate Cancer Cells ◽  
Liver Cancer Cells ◽  
Structure Activity ◽  
Low Cytotoxicity ◽  
Mcf 7

Aims: A series of 8-methoxy ciprofloxacin- hydrazone/acylhydrazone hybrids were evaluated for their activity against a panel of cancer cell lines including HepG2 liver cancer cells, MCF-7, doxorubicin- resistant MCF-7 (MCF-7/DOX) breast cancer cells, DU-145 and multidrug-resistant DU145 (MDR DU-145) prostate cancer cells to seek for novel anticancer agents. Background: Ciprofloxacin with excellent pharmacokinetic properties as well as few side effects, is one of the most common used antibacterial agents. Notably, Ciprofloxacin could induce cancer cells apoptosis, and cell cycle arrest at the S/G2 stage. The structure-activity relationship reveals that the introduction of the methoxy group into the C-8 position of the fluoroquinolone moiety has resulted in a greater binding affinity to the binding site, and 8-methoxy ciprofloxacin derivatives have proved a variety of biological activities even against drug-resistant organisms. However, to the best of our current knowledge, there are no studies that have reported the anticancer activity of 8-methoxy ciprofloxacin derivatives so far. Furthermore, many fluoroquinolone-hydrazone/acylhydrazone hybrids possess promising anticancer activity. Thus, it is rational to screen the anticancer activity of 8-methoxy ciprofloxacin derivatives. Objective: To enrich the structure-activity relationship and provide new anticancer candidates for further investigations. Methods: The desired 8-methoxy ciprofloxacin-hydrazone/acylhydrazone hybrids 5 and 6 were screened for their in vitro anticancer activity against liver cancer cells HepG2, breast cancer cells MCF-7, MCF7/DOX, prostate cancer cells DU-145 and MDR DU-145 by MTT assay. Results: Some of 8-methoxy ciprofloxacin-hydrazone hybrids showed potential activity against HepG2, MCF-7, MCF-7/DOX, DU-145 and MDR DU-145 cancer cell lines, low cytotoxicity towards VERO cells and promising inhibitory activity on tubulin polymerization. Conclusion: Compounds 5d and 5f showed promising anticancer activity, low cytotoxicity, and potential tubulin polymerization inhibitory activity, were worthy of investigation. Other: The structure-activity relationship was enriched.

One-pot green synthesis of acridine alkaloid derivatives and screening of in vitro anticancer activity against Cdc25b and SHP1

2020 ◽  
Vol 17 ◽  
Author(s):  
Hao Li ◽  
Buer Song ◽  
Mamtimin Mahmut ◽  
Mukhtar Imerhasan
Keyword(s):  
Green Synthesis ◽  
Anticancer Activity ◽  
Inhibitory Activity ◽  
Structure Activity Relationship ◽  
Activity Relationship ◽  
One Pot ◽  
Structure Activity ◽  
Dna 2 ◽  
Acridone Derivatives

Aims: To develop of anticancer active pharmaceutical intermediates. Background: Acridone derivatives possesses wide range of pharmacological activities:1) intercalate DNA 2) form covalent bond with DNA. Objective: To Screening of in vitro anticancer activity against Cdc25b and SHP1 of new acridone derivatives and preliminary study on structure-activity relationship. Materials and Methods: Synthesis of new acridone derivatives and in vitro evaluation of their anticancer activity on Cdc25b and SHP1. Natural products that contain acridine structures, such as cystodytin A and acronycine, are isolated from certain marine (tunicates & ascidians, sponges, sea anemones) and plant (bark of Australian scrub ash tree) species. Herein, we report the efficient one-pot green synthesis of twelve novel 3,4-dihydro-1 (2H) acridone derivatives, using montmorillonite K10 as the catalyst and iron/citric acid in water. Also, their inhibitory activity against Cdc25B and SHP1 is examined, in which specific derivatives show enhanced inhibitory activity compared to others. Results and Discussion: Starting from 2-nitrobenzaldehyde derivatives and 1, 3-cyclohexanedione derivatives, twelve new acridone derivatives were prepared and exhibited substantial anticancer activity against Cdc25b and SHP1 cells. Conclusion: Preliminary studies of the structure-activity relationship have shown the influence of the structural parameters and, in particular, the nature of the substituent on aromatic ring structure and cyclohexanone. Other: Further study on structure-activity relationship.

scholarly journals CYTOTOXICITY OF FIVE PLANT EXTRACTS AGAINST DIFFERENT HUMAN CANCER CELL LINES AND THEIR MOLECULAR MECHANISM

2020 ◽  
pp. 194-198
Author(s):  
SALWA EL-HALLOUTY ◽  
ASHWAQ BATAWI ◽  
MANAL SHAFI ◽  
ESAM RASHWAN ◽  
EZZELDIN ELHAWARY ◽  
...  
Keyword(s):  
Cell Lines ◽  
Plant Extracts ◽  
Normal Cell ◽  
Human Cancer ◽  
Human Tumor ◽  
Human Cancer Cell Lines ◽  
Hct 116 ◽  
Bax Gene ◽  
Mcf 7

Objective: Five methanol plant extracts namely, Euphorbia hierosolymitana, Dracaena marginata, Cordyline terminalis, and Sapium sebifera were screened in vitro for their cytotoxic effect on human tumor cell lines; namely, PC-3, HepG-2, HCT-116, and MCF-7 (prostate, liver, colon, and breast cancer) and human normal cell lines, namely, BJ-1. Methods: E. hierosolymitana (extract A) selectively inhibited HCT-116 cell proliferation with IC50 of 4.22 μg/ml, both Dracaena marginata (extract B) (bark, leaves, and branches) showed moderate cytotoxicity on MCF-7 with IC50 of 22.4 and 48.2 μg/ml, respectively. The remaining two extracts showed minimal to insignificant percentage inhibition on all cell lines. Results: E. hierosolymitana extract was selected for further studying, where the effect of the extract on the HCT116 cells showed a downregulation of her2 and Bcl-2 gene and overexpression of the Bax gene. Flow cytometry analysis was also performed to understand the effect of E. hierosolymitana on the apoptosis induction and the cell cycle. The results showed the induction of early and late apoptosis by 5.81 and 10.01%, respectively. Conclusion: Our results infer that E. hierosolymitana has a promising chance in fighting colorectal cancer due to its high cytotoxic effects on HCT116 cancer cells while having minimal effects on the BJ-1 normal cell lines.

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