Browse
Submit Data
Databases
API
Help

Dataset Information

31 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Design, Synthesis and Anticancer Evaluation of Substituted Cinnamic Acid Bearing 2-Quinolone Hybrid Derivatives.

ABSTRACT: A new series of hybrid molecules containing cinnamic acid and 2-quinolinone derivatives were designed and synthesized. Their structures were confirmed by ¹H-NMR, ¹³C-NMR and mass analyses. All the synthesized hybrid molecules were assessed for their in vitro antiproliferative activity against more than one cancer cell lines. Compound 3-(3,5-dibromo-7,8-dihydroxy-4-methyl-2-oxoquinolin-1(2H)-ylamino)-3-phenylacrylic acid (5a) with IC₅₀ = 1.89 μM against HCT-116 was proved to the most potent compound in this study, as compared to standard drug staurosporin. DNA flow cytometry assay of compound 5a revealed G2/M phase arrest and pre-G1 apoptosis. Annexin V-FITC showed that the percentage of early and late apoptosis was increased. The results of topoisomerase enzyme inhibition activity showed that the hybrid molecule 5a displays potent inhibitory activity compared with control.

SUBMITTER: Abu Almaaty AH

PROVIDER: S-EPMC8400797 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Design, synthesis and evaluation of novel cinnamic acid derivatives bearing N-benzyl pyridinium moiety as multifunctional cholinesterase inhibitors for Alzheimer's disease.

Project description:A novel family of cinnamic acid derivatives has been developed to be multifunctional cholinesterase inhibitors against AD by fusing N-benzyl pyridinium moiety and different substituted cinnamic acids. In vitro studies showed that most compounds were endowed with a noteworthy ability to inhibit cholinesterase, self-induced Aβ (1-42) aggregation, and to chelate metal ions. Especially, compound 5l showed potent cholinesterase inhibitory activity (IC50, 12.1 nM for eeAChE, 8.6 nM for hAChE, 2.6 μM for eqBuChE and 4.4 μM for hBuChE) and the highest selectivity toward AChE over BuChE. It also showed good inhibition of Aβ (1-42) aggregation (64.7% at 20 μM) and good neuroprotection on PC12 cells against amyloid-induced cell toxicity. Finally, compound 5l could penetrate the BBB, as forecasted by the PAMPA-BBB assay and proved in OF1 mice by ex vivo experiments. Overall, compound 5l seems to be a promising lead compound for the treatment of Alzheimer's diseases.

| S-EPMC6009898 | biostudies-literature

Design, Synthesis, and Biological Evaluation of 1,2,4-Thiadiazole-1,2,4-Triazole Derivatives Bearing Amide Functionality as Anticancer Agents.

Project description:A novel library of amide functionality having 1,2,4-thiadiazole-1,2,4-triazole (8a-j) analogs was designed, synthesized, and structures were characterized by 1H NMR, 13C NMR, and mass (ESI-MS) spectral data. Further, all compounds were evaluated for their anticancer activities against four different cancer cell lines including breast cancer (MCF-7, MDA MB-231), lung cancer (A549), and prostate cancer (DU-145) by MTT reduction assay method, and etoposide acts as a standard drug. The results confirmed that majority of the synthesized compounds showed moderate to potent anticancer activities aligned with four cell lines. Among the synthesized compounds, 8b, 8c, 8d, 8e, 8g and 8i displayed more potent activity along with inhibitory concentration values ranging from 0.10 ± 0.084 to 11.5 ± 6.49 µM than the standard IC50 values, which ranges from 1.91 ± 0.84 to 3.08 ± 0.135 µM, respectively.

| S-EPMC7243954 | biostudies-literature

Design, synthesis and evaluation of cinnamic acid ester derivatives as mushroom tyrosinase inhibitors.

Project description:Tyrosinase is a key enzyme in melanin biosynthesis, and is also involved in the enzymatic browning of plant-derived foods. Tyrosinase inhibitors are very important in medicine, cosmetics and agriculture. In order to develop more active and safer tyrosinase inhibitors, an efficient approach is to modify natural product scaffolds. In this work, two series of novel tyrosinase inhibitors were designed and synthesized by the esterification of cinnamic acid derivatives with paeonol or thymol. Their inhibitory effects on mushroom tyrosinase were evaluated. Most of these compounds (IC50: 2.0 to 163.8 μM) are found to be better inhibitors than their parent compounds (IC50: 121.4 to 5925.0 μM). Among them, (E)-2-acetyl-5-methoxyphenyl-3-(4-hydroxyphenyl)acrylate (5a), (E)-2-acetyl-5-methoxyphenyl-3-(4-methoxyphenyl)acrylate (5g) and (E)-2-isopropyl-5-methylphenyl-3-(4-hydroxyphenyl)acrylate (6a) showed strong inhibitory activities; the IC50 values were 2.0 μM, 8.3 μM and 10.6 μM, respectively, compared to the positive control, kojic acid (IC50: 32.2 μM). Analysis of the inhibition mechanism of 5a, 5g and 6a demonstrated that their inhibitory effects on tyrosinase are reversible. The inhibition kinetics, analyzed by Lineweaver-Burk plots, revealed that 5a acts as a non-competitive inhibitor while 5g and 6a are mixed-type inhibitors. Furthermore, docking experiments were carried out to study the interactions between 6a and mushroom tyrosinase.

| S-EPMC6071719 | biostudies-literature

Synthesis and potential antimicrobial activity of novel α-aminophosphonates derivatives bearing substituted quinoline or quinolone and thiazole moieties.

Project description:To develop novel antimicrobial agents, and based on the biologically active heterocyclic quinoline and thiazole substituted, a series of novel α-aminophosphonates (9a-h) and (10i-l) derivatives that incorporated quinoline or quinolone, and coumarylthiazole or 5-phenylthiazol-2-amine moieties were designed and synthesized via Kabachnik-Fields reaction in the presence of ionic liquid under ultrasound irradiation. All the new compounds were obtained in good yield with a simple workup and were confirmed using various spectroscopic methods. The in vitro antimicrobial activity of all synthesized compounds were screened in terms of MIC values against the selected strains of Gram-negative and Gram-positive bacteria and two fungal strains using the broth micro-dilution method. The results showed that most of the tested compounds showed moderate inhibitory activities against both Gram-positive and -negative bacteria compared with reference drugs. The following compounds 9e, 9g, 9h, 9i and 9f, 9g, 9h, 10k, 10l are the most active against Gram-positive and Gram-negative bacteria strains, respectively, with MIC values ranging between 0.25 and 128 μg/mL. The synthesized compounds 9b, 9c, 9f, 9g, 9h, 10k, and 10l exhibited excellent antifungal inhibition with MIC values ranging between 0.25 and 32 μg/mL. Structure-activity relationship revealed that the presence of coumarylthiazole moiety and hydroxyl in the quinoline group increased the inhibitory activity against microbial strains pathogens. These results confirm that the synthesized compounds can be potential antimicrobial drugs candidate.

| S-EPMC8560884 | biostudies-literature

Design, Synthesis and Antibacterial Evaluation of 3-Substituted Ocotillol-Type Derivatives.

Project description:Antibiotic resistance has become a serious global problem that threatens public health. In our previous work, we found that ocotillol-type triterpenoid saponin showed good antibacterial activity. Based on preliminary structure-activity relationship, novel serious C-3 substituted ocotillol-type derivatives 7?26 were designed and synthesized. The in vitro antibacterial activity was tested on five bacterial strains (B. subtilis 168, S. aureus RN4220, E. coli DH5?, A. baum ATCC19606 and MRSA USA300) and compared with the tests on contrast. Among these derivatives, C-3 position free hydroxyl substituted compounds 7?14, showed good antibacterial activity against Gram-positive bacteria. Furthermore, compound 22 exhibited excellent antibacterial activity with minimum inhibitory concentrations (MIC) values of 2 ?g/mL against MRSA USA300 and 4 ?g/mL against B. subtilis. The structure-activity relationships of all current ocotillol-type derivatives our team synthesised were summarized. In addition, the prediction of absorption, distribution, metabolism, and excretion (ADME) properties and the study of pharmacophores were also conducted. These results can provide a guide to further design and synthesis works.

| S-EPMC6321515 | biostudies-other

Design, synthesis and bioevaluation of novel 6-substituted aminoindazole derivatives as anticancer agents.

Project description:In the present study, a series of 6-substituted aminoindazole derivatives were designed, synthesized, and evaluated for bio-activities. The compounds were initially designed as indoleamine 2,3-dioxygenase 1 (IDO1) inhibitors based on the structural feature of five IDO1 inhibitors, which are currently on clinical trials, and the important anticancer activity of the indazole scaffold. One of them, compound N-(4-fluorobenzyl)-1,3-dimethyl-1H-indazol-6-amine (36), exhibited a potent anti-proliferative activity with an IC50 value of 0.4 ± 0.3 μM in human colorectal cancer cells (HCT116). This compound also remarkably suppressed the IDO1 protein expression. In the cell-cycle studies, the suppressive activity of compound 36 in HCT116 cells was related to the G2/M cell cycle arrest. Altogether, the current findings demonstrate that compound 36 would be promising for further development as a potential anticancer agent.

| S-EPMC9058813 | biostudies-literature

Design, synthesis, and cytotoxic evaluation of quinazoline derivatives bearing triazole-acetamides.

Project description:A novel series of quinazoline-based agents bearing triazole-acetamides 8a-l were designed and synthesized. All the obtained compounds were tested for in vitro cytotoxic activities against three human cancer cell lines named HCT-116, MCF-7, and HepG2, as well as a normal cell line WRL-68 after 48 and 72 h. The results implied that quinazoline-oxymethyltriazole compounds exhibited moderate to good anticancer potential. The most potent derivative against HCT-116 was 8a (X = 4-OCH3 and R = H) with IC50 values of 10.72 and 5.33 μM after 48 and 72 h compared with doxorubicin with IC50 values of 1.66 and 1.21 μM, respectively. The same trend was seen in the HepG2 cancerous cell line in which 8a recorded the best results with IC50 values of 17.48 and 7.94 after 48 and 72 h, respectively. The cytotoxic analysis against MCF-7 showed that 8f with IC50 = 21.29 μM (48 h) exhibited the best activity, while compounds 8k (IC50 = 11.32 μM) and 8a (IC50 = 12.96 μM), known as the most effective cytotoxic agents after 72 h. Doxorubicin as positive control exhibited IC50 values of 1.15 and 0.82 μM after 48 and 72 h, respectively. Noteworthy, all derivatives showed limited toxicity against the normal cell line. Moreover, docking studies were also presented to understand the interactions between these novel derivatives and possible targets.

| S-EPMC9975091 | biostudies-literature

Targeting matrix metalloproteinases with novel diazepine substituted cinnamic acid derivatives: design, synthesis, in vitro and in silico studies.

Project description:Lung cancer is the notable cause of cancer associated deaths worldwide. Recent studies revealed that the expression of matrix metalloproteinases (MMPs) is extremely high in lung tumors compared with non-malignant lung tissue. MMPs (-2 and -9) play an important part in tumor development and angiogenesis, which suggests that creating potent MMP-2 and -9 inhibitors, should be an important goal in lung cancer therapy. In the present study, an effort has been made to develop new anti-metastatic and anti-invasive agents, wherein a series of novel diazepine substituted cinnamic acid derivatives were designed, synthesized and assayed for their inhibitory activities on MMP-2 and MMP-9. These derivatives were prepared via microwave assisted reaction of tert-butyl (3-cinnamamidopropyl)carbamate derivatives mixed with 2,3-dibromopropanoic acid and potassium carbonate was added to obtain 4-(tert-butoxycarbonyl)-1-cinnamoyl-1,4-diazepane-2-carboxylic acid derivatives. The newly synthesized compounds were characterized by IR, NMR and mass spectroscopy. All the tested compounds showed good to excellent cytotoxic potential against A549 human lung cancer cells. The active compounds displaying good activity were further examined for the inhibitory activity against MMPs (-2 and -9). In addition, the structure and anticancer activity relationship were further supported by in silico docking studies of the active compounds against MMP-2 and MMP-9.

| S-EPMC5910448 | biostudies-literature

Design, synthesis, molecular modelling, and biological evaluation of novel substituted pyrimidine derivatives as potential anticancer agents for hepatocellular carcinoma.

Project description:New anticancer agents are highly needed to overcome cancer cell resistance. A novel series of pyrimidine pyrazoline-anthracene derivatives (PPADs) (4a-t) were designed and synthesised. The anti-liver cancer activity of all compounds was screened in vitro against two hepatocellular carcinoma (HCC) cell lines (HepG2 and Huh-7) as well as normal fibroblast cells by resazurin assay. The designed compounds 4a-t showed a broad-spectrum anticancer activity against the two cell lines and their activity was more prominent on cancer compared to normal cells. Compound 4e showed high potency against HepG2 and Huh-7 cell lines ((IC50=5.34 and 6.13 μg/mL, respectively) comparable to that of doxorubicin (DOX) activities. A structure activity relationship (SAR) has been investigated and compounds 4e, 4i, 4m, and 4q were the most promising anticancer agents against tested cell lines. These compounds induced apoptosis in HepG2 and Huh-7 cells through significant activation of caspase 3/7 at all tested concentrations. In conclusion, 4e could be a potent anticancer drug.

| S-EPMC6537702 | biostudies-literature

Design, synthesis and evaluation of anticancer activity of novel 2-thioxoimidazolidin-4-one derivatives bearing pyrazole, triazole and benzoxazole moieties.

Project description:A novel series of substituted 2-thiohydantoin incorporated with benzoimidazole, pyrazole, triazole and/or benzoxazole moieties has been synthesized using (E)-3-[1-(4-bromophenyl)ethylideneamino]-2-thioxoimidazolidin-4-one 1 as the key starting material. The key material 1 also, reacted with an acetic anhydride, aromatic aldehydes, secondary amines, formaldehyde and triethyl orthoformate to give the corresponding acetyl, chalcone, Mannich bases and ethoxymethylene derivatives, respectively. The structures of the novel compounds were confirmed by spectral data and elemental analysis. The cytotoxic activity of all synthesized compounds was assessed in vitro against human hepatocellular cancer cell line (HePG-2) and breast carcinoma cell line (MCF-7). The bioassay results revealed that compound 14 has the best activity against HePG-2 cell line (IC50 = 2.33 μg/mL), while compound 5 has the best activity against MCF-7 cell line (IC50 = 3.98 μg/mL).

| S-EPMC5940965 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data