Novel isatin–indole derivatives as potential inhibitors of chorismate mutase (CM): their synthesis along with unexpected formation of 2-indolylmethylamino benzoate ester under Pd–Cu catalysis

Reddy, Gangireddy Sujeevan; Hossain, Kazi Amirul; Kumar, J.S. Dileep; Thirupataiah, B.; Edwin, Rebecca Kristina; Giliyaru, Varadaraj Bhat; Hariharapura, Raghu Chandrashekar; Shenoy, Gautham G.; Misra, Parimal; Pal, Manojit

doi:10.1039/c9ra09236f

Cited by 7 publications

(3 citation statements)

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“…We were particularly interested in exploring compounds based on A against chorismate mutase [CM (EC 5.4.99.5) or Mtb CM ( Mycobacterium tuberculosis CM)] [9,10] which is considered as an attractive target for the identification of potential anti‐tubercular agents. This is because the CM inhibition by isatin and its derivatives has been documented in the literature [11,12] …”

Section: Introductionmentioning

confidence: 90%

“…This is because the CM inhibition by isatin and its derivatives has been documented in the literature. [11,12] Over the years, targeting the enzyme CM for the identification of new and potential anti-tubercular agents has become an interesting strategy. [10] This enzyme is known to catalyze the Claisen rearrangement of chorismate to prephenate that is vital for bacterial survival.…”

Section: Introductionmentioning

confidence: 99%

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Synthesis, Docking and In Vitro Evaluation of Spiroindoline‐3,2’‐Quinazoline Derivatives

Addu,

Miriyala,

Kapavarapu

et al. 2023

ChemistrySelect

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The Wang‐OSO3H catalyzed synthesis of a series of spiroindoline‐3,2’‐quinazoline derivatives and their in silico and in vitro evaluation against MtbCM (Mycobacterium tuberculosis Chorismate Mutase) are disclosed. Initially, a library of small molecules based on spiroindoline‐3,2’‐quinazoline framework was constructed. The reaction of 2‐aminobenzamide with appropriate isatin derivatives in the presence of Wang‐OSO3H under ultrasound irradiation was used for this purpose. The reaction proceeded under mild conditions to afford the desired products in good yields within a short duration. With the use of heterogeneous catalyst, inexpensive solvent as reaction media, and ultrasound as the source of green energy the methodology appeared to be a useful alternative to the previously reported methods. The in silico docking of all the synthesized compounds into the MtbCM (PDB: 2FP2) revealed that the binding of these compounds took place on the external surface pockets of the MtbCM active site cavity mainly in two different clusters. Three compounds that interacted well with MtbCM also showed good (57–64 %) inhibition of MtbCM in vitro when tested at 10 μM. Based on in silico and in vitro studies along with the ADME predictions these three spiroindoline‐3,2’‐quinazoline derivatives were identified as pre‐hits.

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Section: Introductionmentioning

confidence: 90%

Section: Introductionmentioning

confidence: 99%

Synthesis, Docking and In Vitro Evaluation of Spiroindoline‐3,2’‐Quinazoline Derivatives

Addu,

Miriyala,

Kapavarapu

et al. 2023

ChemistrySelect

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“…[ 12,13 ] In addition, the NCH linkage, is well known as a building block in organic synthesis evaluated for different kinds of biological activity such as antimicrobial, antifungal, anti‐inflammatory, anti‐cancer, antitumor, and herbicidal. [ 14,15 ] Schiff bases of isatin were reported to possess anti‐HIV, [ 16,17 ] anticonvulsant, [ 18 ] antibacterial, [ 19–22 ] antiprotozoal, [ 23,24 ] antifungal, [ 25–27 ] antiviral, [ 28–30 ] and antituberculosis [ 31–33 ] activity.…”

Section: Introductionmentioning

confidence: 99%

Imino isatin derivatives; synthesis, in silico molecular dynamic study over monoamine oxidase B, ADME prediction, and in vitro cytotoxicity evaluation

Ahmadi

Azizian

2021

J Chinese Chemical Soc

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The monoamine oxidase B (MAO‐B) depicts an attractive drug target for the development of neuro protective agents toward the treatment of neurodegenerative diseases. The current study involved synthesis, in silico and cytotoxic evaluation of N1‐alkylated‐5‐substituted 3‐imino isatin derivatives with the proposed MAO‐B inhibitory activities. The In silico molecular modeling investigation was performed through the induced fit docking, molecular mechanics‐generalized born surface area, and molecular dynamic method in order to uncover the binding mode interaction and their proposed impact on the active site environment and flexibility. The synthesized compounds were characterized by spectroscopic methods. Compound 3‐Imino‐1‐pentyl indolin‐2‐one (3h) with the highest free binding energy adopts an extended conformation spanning from the flavin ring location to the entrance of the substrate cavity. In this way, Ile199 adopts the “open” conformation so the two separate cavities of MAO‐B active site fused and formed a single‐space, which abled the compound extending to the MAO‐B entrance cavity space. From consideration of the data presented in this paper, we reveal that longer N1‐alkylated‐3‐imino isatin derivative could be proposed as inhibitor that would occupy both cavities of the MAO‐B active site. Furthermore, the mentioned derivatives provided acceptable drug profiling based on in silico ADME calculation and MTT cytotoxicity test evaluation.

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Indole: A promising scaffold for the discovery and development of potential anti-tubercular agents

Bajad

Singh

et al. 2022

Current Research in Pharmacology and Drug Discovery

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Novel isatin–indole derivatives as potential inhibitors of chorismate mutase (CM): their synthesis along with unexpected formation of 2-indolylmethylamino benzoate ester under Pd–Cu catalysis

Abstract: Design, synthesis and evaluation of isatin–indole derivatives were undertaken to identify potent inhibitors of chorismate mutase.

Cited by 7 publications

References 36 publications

Synthesis, Docking and In Vitro Evaluation of Spiroindoline‐3,2’‐Quinazoline Derivatives

Synthesis, Docking and In Vitro Evaluation of Spiroindoline‐3,2’‐Quinazoline Derivatives

Imino isatin derivatives; synthesis, in silico molecular dynamic study over monoamine oxidase B, ADME prediction, and in vitro cytotoxicity evaluation

Indole: A promising scaffold for the discovery and development of potential anti-tubercular agents

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