- Design, synthesis and biological evaluation of 8-substituted-6-hydrazonoindolo[2,1-b]quinazolin-12(6H)-one scaffolds as potential cytotoxic agents: IDO-1 targeting molecular docking studies
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Herein, we have reported the synthesis of 18 novel 8-substituted tryptanthrin analogues based on our earlier work. All these tryptanthrin analogues were well characterized by 1H & 13C NMR, FT-IR, Mass Spectrometry and Elemental Analy
- Guda, Ramu,Korra, Rajashekar,Balaji, Siripireddy,Palabindela, Rambabu,Eerla, Rakesh,Lingabathula, Harikiran,Yellu, Narsimha Reddy,Kumar, Girijesh,Kasula, Mamatha
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- Tryptanthrin derivative and preparation thereof and application of tryptanthrin derivative in prevention and treatment of plant viruses and pathogenic bacteria
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The invention relates to tryptanthrin derivatives I-1 to I-7, and a preparation method thereof and application of the tryptanthrin derivatives I-1 to I-7 in prevention and treatment of plant viruses and pathogenic bacteria. The tryptanthrin derivatives I-
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Paragraph 0018; 0032-0033
(2021/06/26)
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- Discovery of Tryptanthrins as Novel Antiviral and Anti-Phytopathogenic-Fungus Agents
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Plant diseases seriously affect the yield and quality of crops and are difficult to control. Tryptanthrin and its derivatives (tryptanthrins) were synthesized and evaluated for their antiviral activities and fungicidal activities. We found that tryptanthrins have good antiviral activities against tobacco mosaic virus (TMV) for the first time. Most of the tryptanthrins showed higher anti-TMV activities than that of ribavirin (inhibitory rates of 40, 37, and 38% at 500 μg/mL for inactivation, curative, and protection activities in vivo, respectively). Compound 3n (inhibitory rates of 52, 49, and 54% at 500 μg/mL for inactivation, curative, and protection activities in vivo, respectively) and compound 14 (inhibitory rates of 51, 48, and 53% at 500 μg/mL for inactivation, curative, and protection activities in vivo, respectively) emerged as new antiviral lead compounds with excellent antiviral activities. Compound 16 was selected for further antiviral mechanism research, which revealed that compound 16 could inhibit virus assembly by decomposing 20S coat protein (CP) disk. Molecular docking results showed that compounds 3n and 14, which have higher antiviral activities in vivo than that of compound 16, do show stronger interaction with TMV CP. Further fungicidal activity tests showed that tryptanthrins displayed broad-spectrum fungicidal activities, especially for compound 16. These compounds showed good selectivity to Physalospora piricola. In the current study, a small molecular library of tryptanthrin was constructed and the bioactivity spectrum of these compounds was broadened, which lays a foundation for their application in plant protection.
- Guo, Jincheng,Hao, Yanan,Li, Yongqiang,Liu, Yuxiu,Ma, Dejun,Wang, Qingmin,Wang, Ziwen
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p. 5586 - 5595
(2020/06/27)
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- 1-Butyl-2-methylpipyridinium iodide ([BMPPY]I): novel ionic liquid for the synthesis of 6-hydroxy-6-(1H-indol-3-yl)indolo[2,1-b]quinazolin-12(6H)-ones under green solvent-free conditions
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Abstract: In this article we reported preparation of 1-butyl-2-methylpipyridinium iodide ([BMPPY]I), as a novel ionic liquid (IL) through simple procedure. This newly prepared IL has been characterized by FT-IR, FESEM, EDX, TGA/DTG, 1H NMR, 13C NMR, and Gc-mass techniques. The FESEM images revealed nano scale for the IL with the average diameter of 150–185?nm. Its efficacy examined for the synthesis of 6-hydroxy-6-(1H-indol-3-yl)indolo[2,1-b]quinazolin-12(6H)-ones via domino three-component reaction of isatin derivatives, isatoic anhydride, and indoles under solvent-free conditions at 100?°C. The results affirmed that ([BMPPY]I) possessed a dual catalytic/solvent role to promote this condensation. Non-flammability, thermal stability, non-toxicity and low cost of the IL that led to obtain pharmaceutically-active heterocycles though easy work-up procedure and short reaction times, are some highlighted features of this green protocol. Graphical abstract: [Figure not available: see fulltext.].
- Nikoofar, Kobra,Peyrovebaghi, Seyedeh Shima
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p. 4287 - 4298
(2019/04/30)
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- Zinc oxide-NP catalyzed direct indolation of: In situ generated bioactive tryptanthrin
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A ZnO-NP catalyzed direct indolation of in situ generated tryptanthrin via C-H functionalization and C-C bond formation has been developed. This novel and greener approach has been effectively utilized to accomplish the synthesis of 6-hydroxy-6-(1H-indol-3-yl)indolo[2,1-b]quinazolin-12(6H)-one derivatives in good to excellent yields with high product selectivity. Besides the in situ approach, a direct indolation of tryptanthrin has also been developed.
- Rai, Byanju,Shukla, Ratnakar Dutt,Kumar, Atul
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p. 822 - 826
(2018/03/02)
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- Design, synthesis, and structure-activity relationship studies of tryptanthrins as antitubercular agents
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The natural product tryptanthrin (1a) represents a potential lead for new tuberculosis (TB) drugs since tryptanthrin and its synthetic analogues possess potent in vitro activity against Mycobacterium tuberculosis (Mtb). However, in spite of their in vitro activity, none of these agents have been shown to be efficacious in vivo against animal models of TB. Described herein are syntheses of new tryptanthrin analogues together with a systematic investigation of their in vitro antitubercular activity and ADME properties followed by pharmacokinetic characterization in rodents for the most promising compounds. Those with the best potency and oral bioavailability were progressed to evaluations of efficacy against acute murine TB. The work aimed to prove the concept that this compound class can limit growth of Mtb during infection as well as to establish the SAR for in vitro activity against Mtb and the range of in vitro ADME parameters for this class of natural products. Novel C-11-deoxy (5b) and A-ring-saturated (6) tryptanthrin analogues were discovered that maintained activity against Mtb and showed improved solubility compared to tryptanthrin as well as evidence of oral bioavailability in rodents. However, neither 5b nor 6 demonstrated efficacy against acute murine TB following administration at doses up to 400 mg/kg daily for 4 weeks. Although 5b and 6 failed to inhibit replication or kill Mtb in vivo, they illuminate a path to new structural variations of the tryptanthrin scaffold that may maximize the potential of this class of compounds against TB.
- Hwang, Jae-Min,Oh, Taegwon,Kaneko, Takushi,Upton, Anna M.,Franzblau, Scott G.,Ma, Zhenkun,Cho, Sang-Nae,Kim, Pilho
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p. 354 - 367
(2013/05/09)
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- Discovery of tryptanthrin derivatives as potent inhibitors of indoleamine 2,3-dioxygenase with therapeutic activity in lewis lung cancer (LLC) tumor-bearing mice
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Indoleamine 2,3-dioxygenase (IDO-1) is emerging as an important new therapeutic target for the treatment of cancer, neurological disorders, and other diseases that are characterized by pathological tryptophan metabolism. However, only a few structural classes are known to be IDO-1 inhibitors. In this study, a natural compound tryptanthrin was discovered to be a novel potent IDO-1 inhibitor by screening of indole-based structures. Three series of 13 tryptanthrin derivatives were synthesized, and the structure-activity analysis was undertaken. The optimization led to the identification of 5c, which exhibited the inhibitory activity at a nanomolar level. In vitro 5c dramatically augmented the proliferation of T cells. When administered to Lewis lung cancer (LLC) tumor-bearing mice, 5c significantly inhibited IDO-1 activity and suppressed tumor growth. In addition, 5c reduced the numbers of Foxp3 + regulatory T cells (Tregs), which are known to prevent the development of efficient antitumor immune responses.
- Yang, Shuangshuang,Li, Xishuai,Hu, Fangfang,Li, Yinlong,Yang, Yunyun,Yan, Junkai,Kuang, Chunxiang,Yang, Qing
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p. 8321 - 8331
(2013/12/04)
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- β-Cyclodextrin catalysed synthesis of tryptanthrin in water
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An efficient and green method has been developed for the synthesis of tryptanthrin employing β-cyclodextrin as a catalyst in aqueous media at room temperature from isatoic anhydride and isatin. The reactions were performed under mild conditions to afford biologically active natural product tryptanthrin in excellent yields.
- Kumar, Atul,Tripathi, Vishwa Deepak,Kumar, Promod
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supporting information; experimental part
p. 51 - 54
(2011/03/20)
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- Antimicrobial activity of tryptanthrins in escherichia coli
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Tryptanthrins have potential therapeutic activity against a wide variety of pathogenic organisms, although little is known about their mechanism. Activity against Escherichia coli, however, has not been examined. The effects of tryptanthrin (indolo[2,1-b]quinazolin-6,12-dione) and nine derivatives on growth, survival, and mutagenesis in E. coli were examined. Analogues with a nitrogen atom at the 4-position of tryptanthrin stopped log phase growth of E. coli cultures at concentrations as low as 5 μM. Tryptanthrins decreased viability during incubation with cells in buffer by factors of 10-2 to -6 at 0.2-40 μM. Derivatives with an oxime group at the 6-position exhibited the greatest bactericidal activity. Most tryptanthrins were not mutagenic in several independent assays, although the 4-aza and 4 aza-8-fluoro derivatives increased frameshift mutations about 22- and 4-fold, respectively. Given the structure of trypanthrins, binding to DNA may occur by intercalation. From analysis using a sensitive linking number assay, several tryptanthrins, especially the 4-aza and 6-oximo derivatives, intercalate into DNA.
- Bandekar, Pooja P.,Roopnarine, Keir Alekseii,Parekh, Virali J.,Mitchell, Thomas R.,Novak, Mark J.,Sinden, Richard R.
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experimental part
p. 3558 - 3565
(2010/07/13)
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- Novel indolo[2,1-b]quinazoline analogues as cytostatic agents: synthesis, biological evaluation and structure-activity relationship.
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In our endeavor to design and synthesize novel anticancer agents, a new series of indoloquinazoline compounds were prepared and tested initially for anticancer activity in vitro against a panel of human cancer cell lines. Most of these compounds exhibited cytotoxic activity in in vitro screens. Compounds were selected and further evaluated using a modified Hollow Fiber Assay for their preliminary in vivo activity against 12 cell lines implanted in the subcutaneous and intraperitoneal compartments in mice. The results indicate that these compounds may constitute a new class of anticancer agents.
- Sharma, Vedula M,Prasanna,Seshu, K V Adi,Renuka,Rao, C V Laxman,Kumar, G Sunil,Narasimhulu, C Prasad,Babu, P Aravind,Puranik,Subramanyam,Venkateswarlu,Rajagopal, Sriram,Kumar, K B Sunil,Rao, C Seshagiri,Mamidi, N V S Rao,Deevi, Dhanvanthri S,Ajaykumar,Rajagopalan
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p. 2303 - 2307
(2007/10/03)
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- Indolo[2,1-biquinazoline-6,12-dione antibacterial compounds and methods of use thereof
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Methods, compounds and compositions are provided form inhibiting the growth of pathogenic mycobacteria in vitro and of treatment of pathogenic mycobacterial infections in vivo using indolo[2,1-b]quinazoline-6,12-dione compounds of the formula (I): STR1 wherein A, B, C, D, E, F, G and H are independently selected from carbon and nitrogen, or A and B or C and D can be taken together to be nitrogen or sulfur, and the pharmaceutically acceptable salts thereof. The methods, compounds and compositons are particularly useful for inhibiting the growth of Mycobacterium tuberculosis, and may be used alone, or in combination with other anti-Mycobacterium tuberculosis agents, such as isoniazid, rifampin, pyrazinamide, rifabutin, streptomycin and ciprofloxacin, to provide new agents for the treatment of tuberculosis, including multidrug-resistant tuberculosis (MDRTB).
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- ANTIMICROBIAL AGENTS FROM HIGHER PLANTS. NEW SYNTHESIS AND BIOACTIVITY OF TRYPTANTHRIN (INDOLO--QUINAZOLIN-6,12-DIONE) AND ITS ANALOGUES.
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Base-catalyzed condensation of substituted isatins and substituted isatoic anhydrides provides a convenient, one-step flexible synthesis of indolo--quinazolin-6,12-diones, including the antifungal natural product tryptanthrin.This new process provides the basis for a systematic exploration of the relationship between structure and antimicrobial activity.Preliminary findings demonstrate that non-symmetrically substituted analogues are easily prepared and the method tolerates the presence of a variety of ring substituents.
- Mitscher, Lester A.,Wong, Wai-Cheong,DeMeulenaere, Teresa,Sulko, Jerzy,Drake, Stephen
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p. 1017 - 1021
(2007/10/02)
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