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Synthesis and antimicrobial evaluation of 2-hydroxynaphthalene-1,4-dione and 4H-chromene conjugates

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Abstract

4H-Chromene and 1,4-naphthoquinone systems are generally considered to be medicinally privileged scaffolds. We have designed novel conjugates that incorporated both these scaffolds, as such conjugates exhibit unique biological properties reflecting those due to individual units and collective presence. In this work, we have achieved facile, efficient, and high yielding synthesis of 19 such conjugates from readily available 2-alkylamino-4-methylsulfanyl-3-nitro-4H-chromenes and 2-hydroxynaphthalene-1,4-dione. Highly polar nitroketene-O,N-acetal unit present in the conjugates is designed to prevent crossing blood brain barrier. We have conducted structure activity relationship (SAR) studies based on initial antimicrobial screening of a set of ten conjugates against three Gram positive bacteria [Bacillus Subtilis, Staphylococcus aureus (MSSA), Staphylococcus aureus (MRSA)], one Gram negative bacteria (Escherichia coli), and two fungi (Aspergillus niger, Candida albicans). The SAR studies revealed that the conjugates with halogens at C(6) and C(8) positions of the 4H-chromene ring having C(2)NMe group display impressive activity, almost equal to that of standard drugs. None of the conjugates, however, showed antimalarial activity, although they possess 2-hydroxy-1,4-naphthoquinone unit.

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Acknowledgments

H.S.P.R. thanks UGC, UGC-SAP, CSIR, and DST-FIST for financial assistance. V.S.T. and L.N.A. thank CSIR for fellowship. We thank Mr. Abdul Kapoor for help in antimicrobial evaluation.

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  1. Department of Chemistry, Pondicherry University, Pondicherry, 605 014, India

    H. Surya Prakash Rao, Venkata Swamy Tangeti & Lakshmi Narayana Adigopula

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  1. H. Surya Prakash Rao
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  2. Venkata Swamy Tangeti
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  3. Lakshmi Narayana Adigopula
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Correspondence to H. Surya Prakash Rao.

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Rao, H.S.P., Tangeti, V.S. & Adigopula, L.N. Synthesis and antimicrobial evaluation of 2-hydroxynaphthalene-1,4-dione and 4H-chromene conjugates. Res Chem Intermed 42, 7285–7303 (2016). https://doi.org/10.1007/s11164-016-2536-5

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