Browsing by Author "Maiti, Barnali"

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Andrographolide downregulates the v-Src and Bcr-Abl oncoproteins and induces Hsp90 cleavage in the ROS-dependent suppression of cancer malignancy
(2014-01-15)
Liu, Sheng-Hung
;
Lin, Chao-Hsiung
;
Liang, Fong-Ping
;
Chen, Pei-Fen
;
Kuo, Cheng-Deng
Andrographolide is a diterpenoid compound isolated from Andrographis paniculata that exhibits anticancer activity. We previously reported that andrographolide suppressed v-Src-mediated cellular transformation by promoting the degradation of Src. In the present study, we demonstrated the involvement of Hsp90 in the andrographolide-mediated inhibition of Src oncogenic activity. Using a proteomics approach, a cleavage fragment of Hsp90 alpha was identified in andrographolide-treated cells. The concentration- and time-dependent induction of Hsp90 cleavage that accompanied the reduction in Src was validated in RK3E cells transformed with either v-Src or a human truncated c-Src variant and treated with andrographolide. In cancer cells, the induction of Hsp90 cleavage by andrographolide and its structural derivatives correlated well with decreased Src levels, the suppression of transformation, and the induction of apoptosis. Moreover, the andrographolide-induced Hsp90 cleavage, Src degradation, inhibition of transformation, and induction of apoptosis were abolished by a ROS inhibitor, N-acetyl-cysteine. Notably, Hsp90 cleavage, decreased levels of Bcr-Abl (another known Hsp90 client protein), and the induction of apoptosis were also observed in human K562 leukemia cells treated with andrographolide or its active derivatives. Together, we demonstrated a novel mechanism by which andrographolide suppressed cancer malignancy that involved inhibiting Hsp90 function and reducing the levels of Hsp90 client proteins. Our results broaden the molecular basis of andrographolide-mediated anticancer activity. (C) 2013 Elsevier Inc. All rights reserved.
Microwave Controlled Reductive Cyclization: A Selective Synthesis of Novel Benzimidazole-alkyloxypyrrolo[1,2-a]quinoxalinones
(2015-05-01)
Dhole, Sandip
;
Selvaraju, Manikandan
;
Maiti, Barnali
;
Chanda, Kaushik
;
Sun, Chung-Ming
An efficient cascade synthesis of novel benzimidazole linked alkyloxypyrrolo[1,2-a]quinoxalinones was explored on soluble polymer support under micro-Wave irradiation. Two exclusive protocols have been developed for the partial and reductive cyclization by Controlling the microwave energy, Commencing from the smile substrate, ortho nitro, pyrrol: carboxylates, N-hydroxy pyrroloquinoxalinones were obtained by,, partial reductive cyclization (60 degrees C, 7 min), and the synthesis of pyrroloquinoxalinones was accomplished by full reductive, cyclization (85 degrees C, 12 min). This method represents the first synthesis N-hydroxy pyrroloquinoxalinones using Pd/C and ammonium formate as reducing agents: Further employing a variety Of alkyl bromides, the obtained pyrroloquinoxalinones were transformed to their corresponding O-, and N-alkylated analogues to deliver the diversified, novel molecular entities.
Microwave-Assisted Linear Approach Toward Highly Substituted Benzo[d]oxazol-5-yl-1H-benzo[d]imidazole on Ionic Liquid Support
(2012-02-01)
Chanda, Kaushik
;
Maiti, Barnali
;
Tseng, Chih-Chung
;
Sun, Chung-Ming
;
應用化學系
A novel and efficient diversity-oriented synthetic approach was employed to access the benzo[d]oxazol-5-yl-1H-, benzo[d]imidazole on ionic liquid support, which helps to absorb microwave irradiation. In this paper, we successfully coupled 4- hydroxy-3-nitrobenzoic acid onto ionic liquid-immobilized o-phenylehediaimine which subsequently underwent an acid mediated, ring closure reaction leading to benzimidazole derivatives. After hydrogenation of the nitro group to an amine, the resulting ionic liquid conjugate was reacted with 1,1-thiocarbonyldiimidazols to yield an ionic liquid tagged-benzoxazol, Final skeletal diversity of the present scaffold was further achieved by S-alkylation with alkyl and aryl bromides. The benzo[d]oxazol-5-, yl-1H-benzo[d]imidazole was finally cleaved smoothly from the ionic liquid support with sodium methoxide in methanol under microwave irradiation. This methodology has provided access to a small, diverse library by straightforward and simple operations and could be applied readily in various drug discovery programs.
Microwave-Enhanced Efficient Regioselective Synthesis of 1,3,4-Trisubstituted 2-Mercaptoimidazoles on a Soluble Support
(2012-01-01)
Yellol, Gorakh S.
;
Chou, Cheng-Ting
;
Chang, Wang-Jin
;
Maiti, Barnali
;
Sun, Chung-Ming
A novel efficient synthetic method for regioselective synthesis of optically active 2-mercaptoimidazoles with three points of structural diversity was investigated on a polyethylene glycol (PEG) support. The key synthetic steps involve (i) synthesis of thiourea derivatives of polymer-supported amino acids with isothiocyanates and (ii) one-pot regioselective condensation of PEG-linked thiourea with a-bromo ketones to furnish the 2-mercaptoimidazole skeleton under microwave conditions. An excellent regioselectivity was observed during this one-pot condensation reaction which was further supported by NOE studies. In addition to three sets of structural diversity, supplementary chirality at the a-position of the 2-mercaptoimidazole skeleton is the key feature of this synthesis. A representative set of 2-mercaptoimidazoles was efficiently assembled on soluble support utilizing various L-amino acids, isothiocyanates and a-bromoaryl ketones with good yields.
Multicomponent Solvent-Free Synthesis Of Benzimidazolyl Imidazo[1,2-a]-pyridine Under Microwave Irradiation
(2013-06-01)
Maiti, Barnali
;
Chanda, Kaushik
;
Selvaraju, Manikandan
;
Tseng, Chih-Chung
;
Sun, Chung-Ming
A novel one-pot, three-component reaction employing variously substituted benzimidazole-linked amino pyridines, aldehydes, and isonitriles catalyzed by scandium(III) triflate under solvent-free conditions were accomplished. This new synthetic methodology facilitates the rapid generation of intricate molecular frameworks in three-dimensional fashion leading to benzinaidazole-imidazo [1,2-a] pyridines. This approach is envisioned as an environmentally benign process and a simple operation to the biological interesting compounds. The present synthetic sequence permits the introduction of three points of structural diversity to expand chemical space with high purity and excellent yields.
Novel approach towards 2-substituted aminobenzimidazoles on imidazolium ion tag under focused microwave irradiation
(2011-08-26)
Chanda, Kaushik
;
Maiti, Barnali
;
Chung, Wen-Sheng
;
Sun, Chung-Ming
;
應用化學系
We have developed an efficient, parallel synthesis of 2-substituted aminobenzimidazoles via intramolecular ring closing reactions of imidazolium ion tag immobilized o-phenylenediamine with various isothiocyanates. The methodology is based on the attachment of 4-fluoro-3-nitro benzoic acid into the imidazolium ion tag, which enables the S(N)Ar reactions with different amines followed by neutral reduction to furnish o-phenylenediamines under microwave irradiation. The substituted isothiocyanates are reacted with o-phenylenediamines to form monothiourea, which is further activated by methyl iodide to undergo desulfurization in one pot manner. The ionic liquid bound 2-substituted aminobenzimidazoles were finally cleaved from the support with sodium methoxide to generate target compounds in good yields and high purities with two points of structural diversity. This synthetic protocol has promising features of extremely short reaction time, operational simplicity, good yields, as well as widespread applications, leading to a facile and straightforward admittance to structurally diverse 2-substituted aminobenzimidazole analogues with potential bioactivities. (C) 2011 Elsevier Ltd. All rights reserved.
Novel approach towards the synthesis of skeletally diverse benzimidazole-pyrrolo[1,2-a]quinoxaline by S(N)Ar/Pictet-Spengler reaction under focused microwave irradiation
(2011-01-01)
Maiti, Barnali
;
Sun, Chung-Ming
;
應用化學系
;
Department of Applied Chemistry
In a study aimed at developing a novel concise approach to the benzimidazole-pyrrolo-[1,2-a]quinoxaline core of medicinal interest, a Pictet-Spengler reaction has been identified that gives direct access to the target compound on soluble polymer support under focused microwave irradiation. The pyrrole moiety has been introduced on polymer immobilized benzimidazole derivatives by S(N)Ar diversification which subsequently transformed to the title compounds via reduction followed by Pictet-Spengler cyclisation with various ketones in good yields and excellent purity. The work described here demonstrates the versatility of the base mediated SNAr reaction coupled with Pictet-Spengler cyclisation in the construction of novel heterocycles.
Novel approach towards the synthesis of skeletally diverse benzimidazole-pyrrolo[1,2-a]quinoxaline by SNAr/Pictet-Spengler reaction under focused microwave irradiation
(2011-01-01)
Maiti, Barnali
;
Sun, Chung-Ming
;
應用化學系
;
Department of Applied Chemistry
In a study aimed at developing a novel concise approach to the benzimidazole-pyrrolo-[1,2-a]quinoxaline core of medicinal interest, a Pictet-Spengler reaction has been identified that gives direct access to the target compound on soluble polymer support under focused microwave irradiation. The pyrrole moiety has been introduced on polymer immobilized benzimidazole derivatives by SNAr diversification which subsequently transformed to the title compounds via reduction followed by Pictet-Spengler cyclisation with various ketones in good yields and excellent purity. The work described here demonstrates the versatility of the base mediated SNAr reaction coupled with Pictet-Spengler cyclisation in the construction of novel heterocycles.
Polymer supported synthesis of novel benzoxazole linked benzimidazoles under microwave conditions: In vitro evaluation of VEGFR-3 kinase inhibition activity
(2011)
Chanda, Kaushik
;
Maiti, Barnali
;
Yellol, Gorakh S.
;
Chien, Ming-Hsien
;
Kuo, Min-Liang
An efficient soluble polymer-supported method has been developed for the parallel synthesis of substituted benzimidazole linked benzoxazoles using focused microwave irradiation. The key step involves the amidation of 4-hydroxy-3-nitrobenzoic acid with polymer-immobilized o-phenylenediamine. Application of mild acidic conditions promoted the ring closure to furnish the benzimidazole ring. After hydrogenation of the nitro-group to amine, the resulted polymer conjugates underwent efficient ring closure with various alkyl, aryl and heteroaryl isothiocyanates to generate the polymer-bound benzimidazolyl benzoxazoles. The polymer-bound compounds were finally cleaved from the support to furnish benzimidazole linked benzoxazole derivatives. The efficacy of the resultant angular bis-heterocyclic library was studied against vascular endothelial growth factor receptor (VEGFR-3). The preliminary screening of these novel compounds exhibits moderate to high inhibition (IC(50) = 0.56-1.42 mM). This protocol provides an easy access to novel angular bis-heterocycles which have potential for the discovery of novel leads for targeted cancer therapeutics.
Traceless Synthesis of Hydantoin Fused Tetrahydro-beta-carboline on Ionic Liquid Support in Green Media
(2009-11-05)
Maiti, Barnali
;
Chanda, Kaushik
;
Sun, Chung-Ming
;
應用化學系
;
Department of Applied Chemistry
A novel ionic liquid (IL) supported, green synthetic protocol has been developed toward the synthesis of oxo and thio hydantoin analogues tethered with tetrahydro-beta-carboline by the use of focused microwave irradiation. IL-bound tryptophan underwent a Pictet-Spengler reaction with various carbonyl compounds to generate the IL-immobilized tetrahydro-beta-carbolines in aqueous isopropanol media. Subsequent reaction of substituted tetra hydro-beta-carboline derivatives with various isocyanates and isothiocyanate provided a three-dimensional combinatorial library in a traceless fashion.