Chemistry of trisindolines: natural occurrence, synthesis and bioactivity

Wati, First Ambar; Santoso, Mardi; Moussa, Ziad; Fatmawati, Sri; Fadlan, Arif; Judeh, Zaher M. A.

doi:10.1039/d1ra03091d

Cited by 15 publications

(17 citation statements)

References 112 publications

(137 reference statements)

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“…This proves that isatin is one of the key intermediates formed under condition‐B. On the other hand, literature study reveals that the acid catalyzed condensation of isatin and indole gives trisindoline [28] which is not formed in our reactions. However, acid catalyzed reaction of isatin and oxindole provides isoindigo [23] .…”

Section: Resultsmentioning

confidence: 54%

Iodine‐DMSO‐Promoted Oxygenation of Indoles: Synthesis of Isatin and Isoindigo

et al. 2022

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Oxygenation/oxidative self-coupling of indole are performed to obtain isatin and isoindigo in the absence of metal catalysts. Iodine-DMSO is used to synthesize isatin whereas Iodine-DMSO-K 2 S 2 O 8 combination is used for isoindigo synthesis directly from indole in a single step. Though several methods are known for isatin synthesis from indole, most of them use large quantity of oxidants or metal catalyzed. Moreover, the primary existing process for the synthesis of isoindigo is the condensation of isatin and oxindole in the presence of an acid catalyst. But this method provides isoindigo derivatives directly from indoles. A plausible mechanism is also proposed based on the various control experiments which indicate that both the reactions proceed via radical route. It is also observed that oxygen atoms of isatin and isoindigo come from water molecule and DMSO.

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Section: Resultsmentioning

confidence: 54%

Iodine‐DMSO‐Promoted Oxygenation of Indoles: Synthesis of Isatin and Isoindigo

et al. 2022

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“…As a result of this surge, numerous methods have been devised for the production of naturally occurring BIMs and their functionalized analogues (see Scheme 1 ). 7 , 11 , 33 , 34 Interestingly, most methods utilize 3-indole aromatic alcohols to afford symmetrical and unsymmetrical 3,3′-BIMs using a condensation strategy with appropriate nucleophiles. 19 , 35 In addition, the most common reaction protocols used in the synthesis include expensive and excess amounts of catalysts such as Cu-catalysts, 36 TsOH, Ga(OTf) 3 , Zn(OTf) 2 , etc.…”

Section: Introductionmentioning

confidence: 99%

“…3,3′-Bisindolylmethane (BIM) and its functionalized class of natural products were originally isolated from cruciferous plants and terrestrial and marine organisms and shown to contain a broad array of medicinal properties. − Key members of this class of natural products include arundine, vibrindole A, streptindole, arsindoline A, tris(1 H -indol-3-yl)methane, and trisindoline (Figure ). − A unique structure of this bioactive intermediate contains two indole units which are responsible for exhibiting a range of essential biological activities such as anti-neurodegenerative, anti-inflammatory, anticancer, antibiotic, insecticidal, antimicrobial, antifungal, and antioxidant properties (Figure ). ,− Interestingly, some of these BIM derivatives are used as a sedatives in the treatment of AIDS, chronic fatigue, irritable bowel syndrome, and cancer, while bis(indolyl)arylmethane-bearing compounds are used as drugs for Parkinson’s disease, obesity, and bacterial and oncolytic viruses. ,− In addition, BIMs have also been found to have the potential to normalize abnormal cell growth associated with cervical dysplasia …”

Section: Introductionmentioning

confidence: 99%

“… − A unique structure of this bioactive intermediate contains two indole units which are responsible for exhibiting a range of essential biological activities such as anti-neurodegenerative, anti-inflammatory, anticancer, antibiotic, insecticidal, antimicrobial, antifungal, and antioxidant properties (Figure ). ,− Interestingly, some of these BIM derivatives are used as a sedatives in the treatment of AIDS, chronic fatigue, irritable bowel syndrome, and cancer, while bis(indolyl)arylmethane-bearing compounds are used as drugs for Parkinson’s disease, obesity, and bacterial and oncolytic viruses. ,− In addition, BIMs have also been found to have the potential to normalize abnormal cell growth associated with cervical dysplasia …”

Section: Introductionmentioning

confidence: 99%

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Effective Synthesis and Biological Evaluation of Natural and Designed Bis(indolyl)methanes via Taurine-Catalyzed Green Approach

et al. 2022

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An ecofriendly, inexpensive, and efficient route for synthesizing 3,3′-bis(indolyl)methanes (BIMs) and their derivatives was carried out by an electrophilic substitution reaction of indole with structurally divergent aldehydes and ketones using taurine and water as a green catalyst and solvent, respectively, under sonication conditions. Using water as the only solvent, the catalytic process demonstrated outstanding activity, productivity, and broad functional group tolerance, affording the required BIM natural products and derivatives in excellent yields (59–90%). Furthermore, in silico based structure activity analysis of the synthesized BIM derivatives divulges their potential ability to bind antineoplastic drug target and spindle motor protein kinesin Eg5. The precise binding mode of BIM derivatives with the ATPase motor domain of Eg5 is structurally reminiscent with previously reported allosteric inhibitor Arry520, which is under phase III clinical trials. Nevertheless, detailed analysis of the binding poses indicates that BIM derivatives bind the allosteric pocket of the Eg5 motor domain more robustly than Arry520; moreover, unlike Arry520, BIM binding is found to be resistant to drug-resistant mutations of Eg5. Accordingly, a structure-guided mechanism of Eg5 inhibition by synthesized BIM derivatives is proposed.

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“…In both naturally occurring and synthetic compounds, indole derivatives are recognized as a privileged structural motif . Statistically, C3-functionalized indole-based compounds are most abundant among all the indole derivatives with various biological activities (Figure a) . 3-Positioned functionalization of the indole ring is a pivotal synthetic route to prepare a number of promising therapeutic agents .…”

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confidence: 99%

DNA-Compatible Diversification of Indole π-Activated Alcohols via a Direct Dehydrative Coupling Strategy

et al. 2022

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Indole-based diversification is highly desired in the DNA-encoded chemical library construction. Herein, we present a general strategy for on-DNA synthesis of diverse C3-functionalized indole derivatives via indole π-activated alcohol formation followed by direct dehydrative coupling. Highly efficient bond linkages of C–C, C–N, and C–S were achieved to fuse building blocks that are widely commercially available. DNA-encoding compatibility of the method has been further demonstrated to pave an avenue for application in constructing indole-focused three-dimensional libraries.

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Chemistry of trisindolines: natural occurrence, synthesis and bioactivity

Abstract: This in-depth review of trisindolines covers their natural occurrence in addition to several routes of synthesis and catalysts used. The biological activities of trisindolines have been discussed with a special emphasis on the structure–activity relationship.

Cited by 15 publications

References 112 publications

Iodine‐DMSO‐Promoted Oxygenation of Indoles: Synthesis of Isatin and Isoindigo

Iodine‐DMSO‐Promoted Oxygenation of Indoles: Synthesis of Isatin and Isoindigo

Effective Synthesis and Biological Evaluation of Natural and Designed Bis(indolyl)methanes via Taurine-Catalyzed Green Approach

DNA-Compatible Diversification of Indole π-Activated Alcohols via a Direct Dehydrative Coupling Strategy

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