Design, Synthesis, and Anticancer Activity of Bis-isoxazole Incorporated Benzothiazole Derivatives
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esign, Synthesis, and Anticancer Activity of Bis-isoxazole Incorporated Benzothiazole Derivatives Purna Koteswara Rao Cherukumallia, Bhaskara Rao Tadiboinaa,*, Kali Charan Gulipallia, Srinu Bodigea, Kiran Gangarapub, and Gattu Sridharc a Department
of Chemistry, Koneru Lakshmaiah Education Foundation, Green Fields, Vaddeswaram, Guntur, 522502 India b School of Pharmacy, Anurag Group of Institutions, Venkatapur, Ghatkaser, Medchal, Telangana, 500088 India c Department of Chemistry, Kakatiya Institute of Technology and Science, Warangal, 506015 India *e-mail: [email protected] Received August 1, 2020; revised September 10, 2020; accepted October 26, 2020
Abstract—A novel series of bis-isoxazole incorporated benzothiazole derivatives has been designed and synthesized. Molecular structures of the compounds have been confirmed by 1H and 13C NMR, and mass spectra. All products have been tested for their in vitro anticancer activity against breast MCF-7 and MDA MB-231, lungs A549, and prostate DU-145 cancer cell lines using the MTT assay and etoposide as a standard drug. Most of the compounds have demonstrated good to moderate activity, and some of those have exhibited more potent activity than etoposide. Keywords: benzothiazole, isoxazole, anticancer activity
DOI: 10.1134/S1070363220100229 INTRODUCTION Heterocyclic compounds, and specifically for the current study benzothiazoles, demonstrate a broad range of biological activities including anticancer [1], antimicrobial [2], antiviral [3], analgesic [4], antimalarial [5], fungicidal [6], antihelmintic [7], antitubercular [8], and many more. For example, molecules of compounds NSC-710305 (1, Fig. 1) and violatinctamine (2, Fig. 1) [9] contain benzothiazole moieties in their structures. Compound 1 demonstrated anticancer activity and has been processed to phase-1 clinical trial [10].
Similarly, 1,2-isoxazoles demonstrated antitumor [11], anti-oxidant [12], antifungal [13], and a range of other activities. One of the anticancer drug candidates Luminespib (3, NVP-AUY922, Fig. 1) contains a synthetic 1,2-isoxazole scaffold [14]. In view of the above and in continuation of the ongoing studies, we have designed and synthesized a new series of bis-isoxazole incorporated benzothiazole derivatives (14a–14j) and confirmed their structures by 1H and 13C NMR, and mass spectra. The products were screened for their anticancer activity towards four human cancer cell lines.
Fig. 1. Structures of anticancer drugs: (a) NSC-710305, 1, (b) Violatinctamine, 2, and (c) NVP-AUY922, 3.
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Table 1. In vitro cytotoxicity of the synthesized compounds 14a–14j (IC50, μM)a Compound 14a 14b 14c 14d 14e 14f 14g 14h 14i 14j Etoposide a Each
MCF-7 3.45±2.67 0.45±0.059 1.29±0.94 7.10±4.56 12.4±6.20 15.3±7.34 0.041±0.0078 0.32±0.061 0.76±0.083 1.52±0.56 2.11 ± 0.024
A549 4.11±2.10 0.10±0.012 1.98±0.33 3.77±2.88 5.69±3.14 Not determined 0.023±0.0056 0.95±0.033 0.33±0.099 1.61±0.48 3.08 ± 0.135
DU-145 ND 1.22±0.72 1.56±0.27 9.94±5.34 4.
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