3,5-Bis(aminopyrimidinyl)indole Derivatives: Synthesis and Evaluation of Pim Kinase Inhibitory Activities

Lee, Jinho; More, Kunal N.; Yang, Seun-Ah; Hong, Victor Sukbong

doi:10.5012/bkcs.2014.35.7.2123

Cited by 13 publications

(6 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The lead molecule also showed binding interaction with Lys67 and Glu89 in the active site of PIM1 (ATP-binding). The structure of an indole-pyrimidine based hybrid is shown in Figure 15, and the in vitro cytotoxicity of compounds 13(b-e) against human cancer cell lines is shown in Table 13 [47].…”

Section: Indole-based Hybridsmentioning

confidence: 99%

Concept of Hybrid Drugs and Recent Advancements in Anticancer Hybrids

et al. 2022

View full text Add to dashboard Cite

Cancer is a complex disease, and its treatment is a big challenge, with variable efficacy of conventional anticancer drugs. A two-drug cocktail hybrid approach is a potential strategy in recent drug discovery that involves the combination of two drug pharmacophores into a single molecule. The hybrid molecule acts through distinct modes of action on several targets at a given time with more efficacy and less susceptibility to resistance. Thus, there is a huge scope for using hybrid compounds to tackle the present difficulties in cancer medicine. Recent work has applied this technique to uncover some interesting molecules with substantial anticancer properties. In this study, we report data on numerous promising hybrid anti-proliferative/anti-tumor agents developed over the previous 10 years (2011–2021). It includes quinazoline, indole, carbazole, pyrimidine, quinoline, quinone, imidazole, selenium, platinum, hydroxamic acid, ferrocene, curcumin, triazole, benzimidazole, isatin, pyrrolo benzodiazepine (PBD), chalcone, coumarin, nitrogen mustard, pyrazole, and pyridine-based anticancer hybrids produced via molecular hybridization techniques. Overall, this review offers a clear indication of the potential benefits of merging pharmacophoric subunits from multiple different known chemical prototypes to produce more potent and precise hybrid compounds. This provides valuable knowledge for researchers working on complex diseases such as cancer.

show abstract

Section: Indole-based Hybridsmentioning

confidence: 99%

Concept of Hybrid Drugs and Recent Advancements in Anticancer Hybrids

et al. 2022

View full text Add to dashboard Cite

show abstract

“…Meridianins have been found to be a family of potent kinase inhibitors against 6 kinases (Table 2) [8] and inhibitory activities of meridianin E over the other 25 purified kinases have been further tested for it is the most active inhibitor against multiple kinases. Meridianin C also showed inhibitory activity towards Pim-1 kinase with an IC 50 value of 1.0 µM and a family of its derivatives substituted at the 3-position and 5-position of the indole were synthesized with potent kinase inhibitory properties against Pim-1 and Pim-3 [22][23][24]. In addition, meridianin C derivatives were prepared as a GSK-3β inhibitor using a structure-based design and the appropriate insertion of compound into the ATP-binding pocket of GSK-3β might lead to a stronger kinase inhibitory activity based on molecular docking analysis [25].…”

Section: Protein Kinase Inhibitory Potenciesmentioning

confidence: 99%

“…An article indicated that meridianin C could significantly suppress the growth of human tongue cancer cell line YD-10B and the antiproliferative function was mediated by micropinocytosis via down-regulation of DKK-3 [44]. Several studies found that meridianin C and its derivatives could inhibit the proliferation of three human leukemia cell lines (MV4-11, K562, and Jurkat) and the mechanism of action might involve pro-apoptosis via regulation of caspase-9, caspase-3, PARP, Mcl-1, Bcl-2, XIAP, eIF-2α and S6 molecules [22,23,45]. In addition, meridianin A, C, D and G showed weak antitumor activity against four human cancer cell lines: A549, DU14, HeLa and MDA-MB-231, in which JAK/STAT3 signaling is hyperactivated [46].…”

Section: Anticancer Effectmentioning

confidence: 99%

A Review: Meridianins and Meridianins Derivatives

Xiao

2022

Molecules

View full text Add to dashboard Cite

Meridianins are a family of indole alkaloids derived from Antarctic tunicates with extensive pharmacological activities. A series of meridianin derivatives had been synthesized by drug researchers. This article reviews the extraction and purification methods, biological activities and pharmacological applications, pharmacokinetic characters and chemical synthesis of meridianins and their derivatives. And prospects on discovering new bioactivities of meridianins and optimizing their structure for the improvement of the ADMET properties are provided.

show abstract

“…A dataset consisting of 57 indole derivatives reported as pim-3 inhibitors were taken for the present study to develop a 3D pharmacophore. The activity of these molecules ranged from 5.295 to 8.187and shared common experimental method [21][22][23]. The structures of these compounds were sketched in Maestro build panel and subsequently prepared using LigPrep module [24,25].…”

Section: Datasetmentioning

confidence: 99%

A Pragmatic Pharmacophore Informatics Strategy to Discover New Potent Inhibitors Against Pim-3

Peddi

Kundenapally

Sivan

et al. 2021

Preprint

View full text Add to dashboard Cite

Pim-3 (proviral integration site moloney murine leukemia virus-3) is an oncogene which encodes proteins belonging to serine/threonine kinase family, and PIM subfamily. It is generally over expressed in epithelial and hematological tumors. It is known to involve in numerous cellular functions such as cell growth, differentiation, survival, tumorigenesis and apoptosis. It also plays a crucial role in regulation of signal transduction cascades. Therefore it emerged as a hopefultherapeutic target for cancer treatment. In current study, indole derivatives having potent inhibitory activity against Pim 3 were taken and pharmacophore based virtual screening was carried out. A five point pharmacophore hypothesis with one hydrogen bond acceptor, one hydrogen bond donor and three aromatic rings i.e., ADRRR was developed with acceptable R2and Q2 values of 0.913 and 0.748 respectively. It was employed as a query and screening was conducted against Asinex and Otava lead library databases to screen out potent drug like candidates. The obtained compounds were subjected to SP, XP docking using 3D model of pim-3 which was constructed through comparative homology modelling and finally binding free energies were calculated for top hits. The docking and binding free energy studies revealed that six hit molecules showed higher binding energy in comparison to the best active molecule. Finally, MD simulations of the top hit with highest binding energy was carried out which indicated that the obtained hit N1 formed a stable complex with pim-3. We believe that these combined protocols will be helpful and cooperative to discover and design more potent pim-3 inhibitors in near future.

show abstract

3,5-Bis(aminopyrimidinyl)indole Derivatives: Synthesis and Evaluation of Pim Kinase Inhibitory Activities

Cited by 13 publications

References 22 publications

Concept of Hybrid Drugs and Recent Advancements in Anticancer Hybrids

Concept of Hybrid Drugs and Recent Advancements in Anticancer Hybrids

A Review: Meridianins and Meridianins Derivatives

A Pragmatic Pharmacophore Informatics Strategy to Discover New Potent Inhibitors Against Pim-3

Contact Info

Product

Resources

About