Synthesis of novel skipped diene-3-halocoumarin conjugates as potent anticancer and antibacterial biocompatible agents

Abstract

Cancer and bacterial infections are persistent nightmares for human health, which are now aggravated by the development of new types of cancer and pathogenic bacteria, as well as their resistance to prescribed drugs. To be part of a hopeful awakening, this work aimed to synthesize four novel skipped diene-3-halocoumarin conjugates coded SDC1-SDC4 and explore their biosafe functions as anticancer and antibacterial alternatives. In the first step of their synthesis, mequinol reacts with ethyl-2-haloacetoacetate through a H₂SO₄-catalyzed Pechmann reaction, yielding 3-halo-6-methoxy-4-methylcoumarins. The in situ-generated Vilsmeier-Haack reagent formylated these trifunctionalized coumarins to create their 7-carbaldehyde congeners. Finally, the target conjugates were prepared by condensing the latter compounds with 2,4-pentadione through the modified Claisen-Schmidt reaction. The molecular structures involving their stereochemistry were established for SDC1-SDC4 by analyzing their spectra released from FTIR, ¹H NMR, ¹³C NMR, and HRMS. On the other hand, the anticancer and cytotoxicity of these conjugates were investigated against eight cancer and three healthy cell lines, respectively, using an MTT-probing technique. Four pathogenic and three commensal aerobes were the microbes utilized to evaluate the antibacterial and microbiota compatibility, respectively, employing a broth microdilution methodology. The results indicated that the conjugate with the highest anticancer attribute and lowest cytotoxicity was SDC1, while SDC2 demonstrated the greatest antibacterial attribute with minimal microbiota toxicity. These findings projected the influence of a 3-position substitute of the coumarin backbone on the biological activities under research. From these, it is concluded that the chemical structures of SDC1 and SDC2 may represent potent anticancer cytocompatible and antibacterial microbiota-compatible scaffolds, respectively.