Synthesis, biological evaluation, in silico docking, and virtual ADME studies of 2-[2-Oxo-3-(arylimino)indolin-1-yl]-N-arylacetamides as potent anti-breast cancer agents

“…SwissADME is a web-based platform that lets users upload or draw their hit compounds with structure or SMILES code. This tool supplies many parameters such as lipophilicity (iLOGP, XLOGP3, WLOGP, MLOGP, SILICOS-IT, Log Po/w), water solubility -Log S (ESOL, Ali, SILICOS-IT), drug-likeness rules (Lipinski, Ghose, Veber, Egan, and Muegge) and Medicinal Chemistry (PAINS, Brenk, Leadlikeness, Synthetic accessibility) methods [39]. The designed novel SARS-CoV-2 RdRp inhibitors were uploaded using SMILES codes and analyzed.…”

Section: Adme Predictionmentioning

confidence: 99%

Pyrazine-chromene-3-carbohydrazide conjugates: Molecular docking and ADMET predictions on dual-acting compounds against SARS-CoV-2 Mpro and RdRp

Mermer¹,

Vakal²

2021

jrp

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Drug discovery campaigns against COVID-19 lag far behind vaccine development, but given the low vaccine production rate and unfair distribution, there is still an urgent need to advance reliable and potent anti-SARS-CoV-2 agents. We aimed to identify novel and effective molecules with dual-target activity against SARS-CoV-2 main protease (M pro ) and RNA-dependent RNA-polymerase (RdRp). For this, we designed and evaluated the library of hybrid compounds based on pyrazine and 4H-chromen-4-one linked by amide bridges. The synthetic availability of the compounds ranged from 3.08 to 3.40, indicating that these compounds are easy to synthesize. According to in silico ADMET prediction, most of the compounds satisfied all rules of drug-likeness. Compounds CPC-2, 3, 4, 8, 10, 11-14, and 16 were CYP1A2, CYP2C9, and CYP3A4 inhibitors, whereas none of them inhibited CYP2C19 and CYP2D6 isoforms. All designed compounds were predicted to be well-absorbed in the GI tract but not blood-brain barrier permeant and not subject to active efflux.Molecular docking studies against SARS-CoV-2 M pro showed that compounds CPC-1, 6, 7, 8, and 10 could establish multiple H-bonds with the binding site residues. In the case of SARS-CoV-2 RdRp, compounds 6,8,13,14,and 16 had the most favorable binding orientations and could establish H-bonds, pi-cation, and salt-bridges with the binding tunnel residues and RNA. Compound CPC-6 turned to be the most promising candidate from the dual-action side since it had reasonable docking scores and MM-GBSA ∆Gbind values, and good interaction profiles for both M pro and RdRp.

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“…Incorporation of amide into N‐1 position of isatin moiety was also tolerated and hybrids 10 (GI 50 : <0.02–0.21 μM, SRB assay) exhibited promising activity against MCF‐7 cancer cells and molecular docking studies showed that these hybrids could inhibit EGFR effectively. [ 44–47 ] The SAR demonstrated that chloro at R 1 position and methyl at R 2 position could boost up the activity. Particularly, the activity of hybrids 10a–d (GI 50 : <0.02 μM, total growth inhibition [TGI]: 0.07–0.09 μM) was on the same level with that of doxorubicin (GI 50 : <0.02 μM, TGI: 0.02 μM) against MCF‐7 cancer cells.…”

Section: Isatin–coumarin Hybridsmentioning

confidence: 99%

“…Incorporation of amide into N-1 position of isatin moiety was also tolerated and hybrids 10 (GI 50 : <0.02-0.21 μM, SRB assay) exhibited promising activity against MCF-7 cancer cells and molecular docking studies showed that these hybrids could inhibit EGFR effectively. [44][45][46][47] The SAR demonstrated that chloro at R 1 position and methyl at R 2 position could boost up the activity.…”

Section: Isatin-imine Hybridsmentioning

confidence: 99%

Recent advances in isatin hybrids as potential anticancer agents

Ding

Zhou

Zeng

2020

Archiv der Pharmazie

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The isatin framework is a useful template for the development of novel anticancer agents. This is exemplified by the fact that several isatin‐based anticancer agents, such as semaxanib, sunitinib, nintedanib, and hesperadin, are already in use or under clinical trials for the treatment of diverse kinds of cancers. Isatin‐based hybrids could be obtained by incorporating other anticancer pharmacophores into the isatin skeleton and they have the potential to overcome drug resistance with reduced side effects. Thus, isatin‐based hybrids may provide attractive scaffolds for the development of novel anticancer agents. This review covers the recent advances of isatin‐based hybrids with anticancer activity, covering articles published between 2001 and 2019. The anticancer activities of these molecules and the structure–activity relationships are also discussed. The purpose of this review article is to set up the direction for the design and development of isatin‐based hybrids with high efficacy and low toxicity.

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Synthesis, biological evaluation, in silico docking, and virtual ADME studies of 2-[2-Oxo-3-(arylimino)indolin-1-yl]-N-arylacetamides as potent anti-breast cancer agents

Cited by 26 publications

References 37 publications

Isatin and its derivatives: a survey of recent syntheses, reactions, and applications

Isatin and its derivatives: a survey of recent syntheses, reactions, and applications

Pyrazine-chromene-3-carbohydrazide conjugates: Molecular docking and ADMET predictions on dual-acting compounds against SARS-CoV-2 Mpro and RdRp

Recent advances in isatin hybrids as potential anticancer agents

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