Novel indole derivatives as potential anticancer agents: Design, synthesis and biological screening

Prakash, B.; Amuthavalli, A.; Edison, David; Sivaramkumar, M. S.; Velmurugan, Rajendran

doi:10.1007/s00044-017-2065-9

Cited by 25 publications

(9 citation statements)

References 28 publications

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“…It is found in many natural and synthetic compounds including anticancer agents [ 43 ] ( Figure 1 b). Such compounds were found to act as antitumor agents via different MOAs [ 44 ] i.e., antimitotic agents (i.e., Vincristine), histone deacetylases (HDACs) (i.e., Panobinostat), PIM kinases (i.e., DHPCC-9), and DNA topoisomerases (i.e., β-carboline).…”

Section: Introductionmentioning

confidence: 99%

Design, Synthesis, Molecular Modeling and Antitumor Evaluation of Novel Indolyl-Pyrimidine Derivatives with EGFR Inhibitory Activity

et al. 2021

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Scaffolds hybridization is a well-known drug design strategy for antitumor agents. Herein, series of novel indolyl-pyrimidine hybrids were synthesized and evaluated in vitro and in vivo for their antitumor activity. The in vitro antiproliferative activity of all compounds was obtained against MCF-7, HepG2, and HCT-116 cancer cell lines, as well as against WI38 normal cells using the resazurin assay. Compounds 1–4 showed broad spectrum cytotoxic activity against all these cancer cell lines compared to normal cells. Compound 4g showed potent antiproliferative activity against these cell lines (IC50 = 5.1, 5.02, and 6.6 μM, respectively) comparable to the standard treatment (5-FU and erlotinib). In addition, the most promising group of compounds was further evaluated for their in vivo antitumor efficacy against EAC tumor bearing mice. Notably, compound 4g showed the most potent in vivo antitumor activity. The most active compounds were evaluated for their EGFR inhibitory (range 53–79 %) activity. Compound 4g was found to be the most active compound against EGFR (IC50 = 0.25 µM) showing equipotency as the reference treatment (erlotinib). Molecular modeling study was performed on compound 4g revealed a proper binding of this compound inside the EGFR active site comparable to erlotinib. The data suggest that compound 4g could be used as a potential anticancer agent.

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Section: Introductionmentioning

confidence: 99%

Design, Synthesis, Molecular Modeling and Antitumor Evaluation of Novel Indolyl-Pyrimidine Derivatives with EGFR Inhibitory Activity

et al. 2021

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“…Several isatin-hydrazine hybrid structures presented good antitumor activities against cancer cell lines such as breast, lung and leukemia ( Abdel-Aziz et al, 2012 ; Azizian et al, 2012 ; Dweedar et al, 2014 ; Eldehna et al, 2015 ; Prakash et al, 2018 ). Derivatives of [(3-indolylmethylene)hydrazono]indolin-2-one (II, Figure 5 ), for example, were tested against breast cell lines (MCF-7, MDA-MB-231).…”

Section: Isatin-derivatives As Anticancer Agentsmentioning

confidence: 99%

Anticancer Compounds Based on Isatin-Derivatives: Strategies to Ameliorate Selectivity and Efficiency

Paiva

Vieira

Silva

et al. 2021

Front. Mol. Biosci.

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In this review we compare and discuss results of compounds already reported as anticancer agents based on isatin-derivatives, metalated as well as non-metallated. Isatin compounds can be obtained from plants, marine animals, and is also found in human fluids as a metabolite of amino acids. Its derivatives include imines, hydrazones, thiosemicarbazones, among others, already focused on numerous anticancer studies. Some of them have entered in pre-clinical and clinical tests as antiangiogenic compounds or inhibitors of crucial proteins. As free ligands or coordinated to metal ions, such isatin derivatives showed promising antiproliferative properties against different cancer cells, targeting different biomolecules or organelles. Binding to metal ions usually improves its biological properties, indicating a modulation by the metal and by the ligand in a synergistic process. They also reveal diverse mechanisms of action, being able of binding DNA, generating reactive species that cause oxidative damage, and inhibiting selected proteins. Strategies used to improve the efficiency and selectivity of these compounds comprise structural modification of the ligands, metalation with different ions, syntheses of mononuclear and dinuclear species, and use of inserted or anchored compounds in selected drug delivery systems.

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“…Besides the abovementioned indole–pyrimidine hybrids, some other indole derivatives bearing pyrimidine moiety also possessed a certain antibacterial activity. [ 162–169 ] However, the majority of them were far less potent than the reference drugs. Despite this, the SAR was enriched and the enriched SAR may pave the way for further rational design.…”

Section: Indole–pyridine/pyrimidine Hybridsmentioning

confidence: 99%

Indole/isatin‐containing hybrids as potential antibacterial agents

Song

Bian

et al. 2020

Archiv der Pharmazie

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The emergence and worldwide spread of drug-resistant bacteria have already posed a serious threat to human life, creating the urgent need to develop potent and novel antibacterial drug candidates with high efficacy. Indole and isatin (indole-2,3-dione) present a wide structural and mechanistic diversity, so their derivatives possess various pharmacological properties and occupy a salient place in the development of new drugs. Indole/isatin-containing hybrids, which demonstrate a promising activity against a panel of clinically important Gram-positive and Gram-negative bacteria, are privileged scaffolds for the discovery of novel antibacterial candidates. This review, covering articles published between January 2015 and May 2020, focuses on the development and structure-activity relationship (SAR) of indole/isatincontaining hybrids with potential application for fighting bacterial infections, to facilitate further rational design of novel drug candidates.

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Novel indole derivatives as potential anticancer agents: Design, synthesis and biological screening

Cited by 25 publications

References 28 publications

Design, Synthesis, Molecular Modeling and Antitumor Evaluation of Novel Indolyl-Pyrimidine Derivatives with EGFR Inhibitory Activity

Design, Synthesis, Molecular Modeling and Antitumor Evaluation of Novel Indolyl-Pyrimidine Derivatives with EGFR Inhibitory Activity

Anticancer Compounds Based on Isatin-Derivatives: Strategies to Ameliorate Selectivity and Efficiency

Indole/isatin‐containing hybrids as potential antibacterial agents

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