Synthesis and cytotoxic activity of novel 3-(1H-indol-3-yl)-1H-pyrazole-5-carbohydrazide derivatives

Zhang, Datong; Wang, Guangtian; Zhao, Guilong; Xu, Weifeng; Huo, Lingyan

doi:10.1016/j.ejmech.2011.09.049

Cited by 33 publications

(12 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Cell permeability, in turn, depends on the partition coefficient and water solubility a compound. The designed analogs (SGS-2, 3,6,8,12,13,14) have shown octanol and water (log Po/w<5) and analogs (SGS-2, 3,5,7,8,12,13,14) have solubility (QPlogS: -6.5 to 0.5) coefficient values in an acceptable range.…”

Section: Resultsmentioning

confidence: 99%

“…Pyrazole analogs have shown significant biological activities such as antipyretic, anti-inflammatory, analgesic, antimicrobial [12], anticancer [13], monoamine oxidative inhibitory [14] and various other activities. Recent reports revealed that a pyrazole analog lersivirine had been reported as a nonnucleoside reverse transcriptase inhibitor [15].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

A Battle Against Aids: New Pyrazole Key to an Older Lock-Reverse Transcriptase

Jacob

Ganguly

2016

Int J Pharm Pharm Sci

View full text Add to dashboard Cite

Objective: The reason for the failure of most of the anti-HIV drugs are their poor pharmacokinetics, the poor risk to benefit ratio and the drug resistance. With the objective of developing newer pyrazole scaffolds for effective treatment of HIV, binding mode analysis of designing ligands with the HIV-1RT protein and prediction of key ADME and toxicity parameters of the compounds was in an area of interest. Methods:In this study, molecular docking studies and ADME-T studies were carried out in designing of some novel pyrazole analogs. The protein (PDB ID: 1RT2) was prepared using the Protein Preparation Wizard (Schrodinger Glide 5.0). ADME parameters calculated by QikProp 3.0v and toxicity of designed analogs checked by using two different online software's namely Lazar and protox.Results: Most of the designed pyrazole analogs have good oral absorption as well as good binding affinity towards HIV-1 reverse transcriptase. Conclusion:Finally total 5 analogs (SGS-2, 3, 12, 13 and 14) from the 14 designed leads were found to be best on the basis of molecular docking and ADME-T studies.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A Battle Against Aids: New Pyrazole Key to an Older Lock-Reverse Transcriptase

Jacob

Ganguly

2016

Int J Pharm Pharm Sci

View full text Add to dashboard Cite

show abstract

“…They display a wide spectrum of biological activities including anticancer activity. [32][33][34] Combining the structural features of two differing pharmacophores is an effective tactic in medicinal chemistry, as new bioactive, chemotherapeutic chemical entities characterized by a reduced risk of drug-drug interactions and improved anticancer profiles can be obtained. [35][36][37] Considering the structural characteristics of isatin and indole, merging these two bioactive moieties into a single compound through a carbohydrazide bridge is predicted to result in new promising anticancer leads.…”

Section: Introductionmentioning

confidence: 99%

<p>New Isatin–Indole Conjugates: Synthesis, Characterization, and a Plausible Mechanism of Their in vitro Antiproliferative Activity</p>

Al-Wabli

Almomen

Almutairi

et al. 2020

DDDT

View full text Add to dashboard Cite

Background: Cancer remains the leading cause of human morbidity universally. Hence, we sought to assess the in vitro antiproliferative activity of new isatin-based conjugates (5a-s) against three human cancer cell lines. Methods: The antiproliferative activities of compounds 5a-s were evaluated in vitro and their ADME (absorption, distribution, metabolism and excretion) was carried out using standard protocols. Subsequently, Western blot analysis was conducted to elucidate the potential antiproliferative mechanism of compounds 5a-s. Results: The in vitro antiproliferative activities of compounds 5a-s against the tested cancer cell lines ranged from 20.3 to 95.9%. Compound 5m had an IC 50 value of 1.17 µM; thus, its antiproliferative potency was approximately seven-fold greater than that of sunitinib (IC 50 = 8.11 µM). In-depth pharmacological testing was conducted with compound 5m to gain insight into the potential antiproliferative mechanism of this class of compounds. Compound 5m caused an increase in the number of cells in the G1 phase, with a concomitant reduction of those in the G2/M and S phases. Additionally, compound 5m significantly and dose-dependently reduced the amount of phosphorylated retinoblastoma protein detected. Compound 5m enhanced expression of B cell translocation gene 1, cell cycle-associated proteins (cyclin B1, cyclin D1, and phosphorylated cyclin-dependent kinase 1), and a pro-apoptotic protein (Bcl-2-associated X protein gene), and activated caspase-3. ADME predictions exposed the oral liability of compounds 5a-s. Conclusion: Herein, we revealed the antiproliferative activity and ADME predictions of the newly-synthesized compounds 5a-s and provided a detailed insight into the pharmacological profile of compound 5m. Thus, compounds 5a-s can potentially be exploited as new antiproliferative lead compounds for cancer chemotherapeutic.

show abstract

“…Development of drug and multidrug-resistance (MDR) represents a major problem in which cancer cells become concurrently resistant to different types of chemotherapeutic agents [ 6 , 7 , 8 , 9 ]. Hence, the finding and identification of new safe, effective anticancer agents are a very important goal in medicinal chemistry [ 10 , 11 , 12 ], and it was necessary to try new chemical entities as potential chemotherapeutic agents with another mechanism of action. Diamides derivatives received important attention for their antitumor activities, particularly for those having a basic diamide scaffold and pharmacophores [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

The Design and Development of Potent Small Molecules as Anticancer Agents Targeting EGFR TK and Tubulin Polymerization

Ihmaid

Ahmed

Zayed

2018

IJMS

View full text Add to dashboard Cite

Some novel anthranilate diamides derivatives 4a–e, 6a–c and 9a–d were designed and synthesized to be evaluated for their in vitro anticancer activity. Structures of all newly synthesized compounds were confirmed by infra-red (IR), high-resolution mass (HR-MS) spectra, 1H nuclear magnetic resonance (NMR) and 13C nuclear magnetic resonance (NMR) analyses. Cytotoxic screening was performed according to (3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide) tetrazolium (MTT) assay method using erlotinib as a reference drug against two different types of breast cancer cells. The molecular docking study was performed for representative compounds against two targets, epidermal growth factor receptor (EGFR) and tubulin in colchicine binding site to assess their binding affinities in order to rationalize their anticancer activity in a qualitative way. The data obtained from the molecular modeling was correlated with that obtained from the biological screening. These data showed considerable anticancer activity for these newly synthesized compounds. Biological data for most of the anthranilate diamide showed excellent activity with nanomolar or sub nanomolar half maximal inhibitory concentration (IC50) values against tumor cells. EGFR tyrosine kinase (TK) inhibition assay, tubulin inhibition assay and apoptosis analysis were performed for selected compounds to get more details about their mechanism of action. Extensive structure activity relationship (SAR) analyses were also carried out.

show abstract

Synthesis and cytotoxic activity of novel 3-(1H-indol-3-yl)-1H-pyrazole-5-carbohydrazide derivatives

Cited by 33 publications

References 20 publications

A Battle Against Aids: New Pyrazole Key to an Older Lock-Reverse Transcriptase

A Battle Against Aids: New Pyrazole Key to an Older Lock-Reverse Transcriptase

<p>New Isatin–Indole Conjugates: Synthesis, Characterization, and a Plausible Mechanism of Their in vitro Antiproliferative Activity</p>

The Design and Development of Potent Small Molecules as Anticancer Agents Targeting EGFR TK and Tubulin Polymerization

Contact Info

Product

Resources

About