Design and Synthesis of Imidazo[2,1‐<i>b</i>]thiazole–Chalcone Conjugates: Microtubule‐Destabilizing Agents

Kamal, Ähmed; Balakrishna, Moku; Nayak, V. Lakshma; Shaik, Thokhir Basha; Faazil, Shaikh; Nimbarte, Vijaykumar D.

doi:10.1002/cmdc.201402310

Cited by 34 publications

(13 citation statements)

References 68 publications

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“…The compounds 4-9 showed promising antiproliferative activity with IC 50 ≤ 5 µM while as the compounds 10-14 depicted IC 50 ≥ 8 µM against given cell lines. As per the literature survey, the anti-proliferative activity of the steroidal imidazopyridines (4-9) is consistent with the activity shown by already known non steroidal imidazopyridines [42,43]. The prominent anti-proliferative activity of compound 4-9 may be due to the presence of phenyl moiety of phenylamino/ benzylamino groups in them.…”

Section: In Vitro Cytotoxicitysupporting

confidence: 83%

Synthesis of new steroidal imidazo [1,2-a] pyridines: DNA binding studies, cleavage activity and in vitro cytotoxicity

2015

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Section: In Vitro Cytotoxicitysupporting

confidence: 83%

Synthesis of new steroidal imidazo [1,2-a] pyridines: DNA binding studies, cleavage activity and in vitro cytotoxicity

2015

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“…Kamal et al [32] also designed a novel series of imidazole merged with thiazole as chalcone-like derivatives and evaluated their cytotoxic activity against MCF-7, A549, HeLA, DU-145, and HT-29 cell lines. Among the compounds tested, structure 13 (Figure 4) with a pyridyl ring was the most active.…”

Section: Fused Thiazole Rings Decorated With Different Fragmentsmentioning

confidence: 99%

Thiazole Moiety: An Interesting Scaffold for Developing New Antitumoral Compounds

Ramos-Inza¹,

Aydillo²,

Sanmartín³

et al. 2020

Heterocycles - Synthesis and Biological Activities

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Currently, cancer is one of the major health problems of the human population and prominent cause of death. Thiazole ring has demonstrated many pharmacological activities including anticancer. This scaffold has been found alone or incorporated into the diversity of therapeutic active agents such as tiazofurin, dasatinib, and bleomycin, which are well-known antineoplastic drugs. Recently, most of the compounds isolated from natural sources containing thiazole moiety exhibit notable cytotoxicities and present antitumor potential. In this context, several structural changes have been made in the original structure, such as the incorporation of different substituents or the fusion with other carbo-and heterocycles, in order to increase the antitumoral potency. Related to mechanism of action of these derivatives, some of them act through kinase modulation, polymerization inhibition of microtubule, pro-matrix metalloproteinase activation, signal transducer activation of transcription 3, histone deacetylase inhibition, etc.

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“…To further elucidate the mechanism of 5-indolyl-7-arylimidazo[1,2- a ]pyridine-8-carbonitrile derivatives interfering with microtubule formation, a competition binding assay was employed to examine whether the selected 5k directly binds to the colchicine site. As reported, competition between the test compound and colchicine for the binding site will decrease the intrinsic fluorescence of colchicine-tubulin complex by reducing the amount of colchicine bound, which could be used as an index for 5k competition with colchicine in tubulin binding 37 . As depicted in Fig.…”

Section: Resultsmentioning

confidence: 94%

Discovery and Optimization of Novel 5-Indolyl-7-arylimidazo[1,2-a]pyridine-8-carbonitrile Derivatives as Potent Antitubulin Agents Targeting Colchicine-binding Site

Zhai

Wang

et al. 2017

Sci Rep

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Aiming at development of potent antitubulin agents targeting colchicine-binding site, a series of novel 5-indolyl-7-arylimidazo[1,2-a]pyridine-8-carbonitrilederivatives (5a–5v and 7a–7h) were designed based on bioisosterism and hybridization strategies. All these compounds were concisely synthesized via a three-step process and examined against five human cancer cell lines (HT-29, A549, MKN-45, MDA-MB-231 and SMMC-7721) along with a normal human cell (L02) in vitro. A structure-activity relationships (SARs) study was carried out and optimization towards this series of compounds in cellular assay resulted in the discovery of 5k, which displayed similar or better antitumor potency against the tested cancer cells with IC50 value ranging from 0.02 to 1.22 μM superior to CA-4 and Crolibulin. Significantly, a cell cycle study disclosed the ability of 5k to arrest cell cycle at the G2/M phase, and immunofluorescence assay as well as a colchicine competition assay revealed that tubulin polymerization was disturbed by 5k by binding to the colchicine site. Moreover, the molecular modeling mode showed the posture of 5k and Crolibulin was similar in the colchcine-binding pocket of tubulin as identified with the SARs and pharmacological results. Together, all these results rationalized 5k might serve as a promising lead for a novel class of antitubulin agents for cancer treatments.

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Design and Synthesis of Imidazo[2,1‐b]thiazole–Chalcone Conjugates: Microtubule‐Destabilizing Agents

Cited by 34 publications

References 68 publications

Synthesis of new steroidal imidazo [1,2-a] pyridines: DNA binding studies, cleavage activity and in vitro cytotoxicity

Synthesis of new steroidal imidazo [1,2-a] pyridines: DNA binding studies, cleavage activity and in vitro cytotoxicity

Thiazole Moiety: An Interesting Scaffold for Developing New Antitumoral Compounds

Discovery and Optimization of Novel 5-Indolyl-7-arylimidazo[1,2-a]pyridine-8-carbonitrile Derivatives as Potent Antitubulin Agents Targeting Colchicine-binding Site

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