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Vol. 36 No. 2 (2024): Vol 36 Issue 2, 2024

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Synthesis of Unusually Substituted 2,4,5-Trimethoxy 3,5-Diaryl Isoxazoles from Natural Precursor: Antimicrobial and Anticancer Activities

https://doi.org/10.14233/ajchem.2024.31015
M.V. Ravindra
Department of Nanotechnology, Center for Post Graduate Studies, Visvesvaraya Technological University, Muddenahalli, Bengaluru Region- 562101, India
https://orcid.org/0009-0000-6395-204X
S. Suvarna
Vittal Mallya Scientific Research Foundation, 2/1, J.C. Industrial Layout, Yelechenahalli, Kanakapura Road, Bangalore-560078, India
https://orcid.org/0009-0004-0906-3793
C.S. Ananda Kumar
Department of Nanotechnology, Center for Post Graduate Studies, Visvesvaraya Technological University, Muddenahalli, Bengaluru Region- 562101, India
https://orcid.org/0009-0000-2492-4644

Corresponding Author(s) : M.V. Ravindra

ravimvr1@gmail.com

Asian Journal of Chemistry, Vol. 36 No. 2 (2024): Vol 36 Issue 2, 2024

Abstract

In this work, 2,4,5-trimethoxy substituted 3,5-diaryl isoxazoles were synthesized via their chalcone intermediates and evaluated for antimicrobial and anticancer activities. The natural precursor 2,4,5-trimethoxy benzaldehyde (asaronaldehyde) was obtained from oxidation of β-asarone (Acorus calamus oil) and then reacted with substituted acetophenones via Claisen-Schmidt condensation yielded 2,4,5-trimethoxy substituted chalcones. These chalcones on further treatment with hydroxylamine in presence of sodium acetate and acetic acid cyclizes to give the corresponding 3,5-diaryl isoxazoles yields ranging from 65-80%. Structures were confirmed by IR, GC-MS, 1H NMR and 13C NMR. Synthesized compounds were screened for their antimicrobial activity against bacteria and fungi. The para-substituted isoxazoles (5b, 5c and 5d) exhibited good activity against Gram-negative (Escherichia coli) and (Pseudomonas aeruginosa) and Gram-positive (Bacillus subtilis) and Bacillus licheniformis bacteria and fungi (Phytophthora capsici, Sclerotirum rolfsii, Aspergillus niger and Alternaria alternate). Further, these novel analogues were evaluated for their in vitro anticancer activity against three human tumor cell lines (MCF-7, SW-982 and HeLa) using MTT assay. The anticancer results revealed that phenyl ring at C-3 position bearing electron donor groups in the para-position and 2,4,5-trimethoxy substitutent of the phenyl ring at C-5 position isoxazole showed better inhibitory activity (5b, 5c and 5d). Among synthesized isoxazoles due to the hyper conjugative effect, 2,4,5-trimethoxy 3,5-diaryl isoxazole (5g) having 3-triflouromethyl substitution showed good antimicrobial and higher inhibitory IC50 values 8.56 ± 0.32, 12.16 ± 0.86 and 10.16 ± 0.68 μg/mL (p < 0.05) respectively, when compared to natural precursor β-asarone.

Keywords

β-Asarone Asaronaldehyde Chalcones Isoxazoles Antimicrobial activity Anticancer activity
Ravindra, M., Suvarna, S., & Ananda Kumar, C. (2024). Synthesis of Unusually Substituted 2,4,5-Trimethoxy 3,5-Diaryl Isoxazoles from Natural Precursor: Antimicrobial and Anticancer Activities. Asian Journal of Chemistry, 36(2), 458–464. https://doi.org/10.14233/ajchem.2024.31015
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