Synthesis of some 1,4-naphthoquinones and reactions relating to their use in the study of bacterial growth inhibition

Abstract

A series of 107 1,4-naphthoquinones and related products has been synthesized to study their mode of action in bacterial growth inhibition. The itz vitro reactions of a number of these with aniline, 11-butylamine, sodium methoxide, and an 11-buthanethiol -triethylamine mixture have been examined. A series of epoxides of C-2 monosubstituted and C-2,C-3 disubstituted 1,4-naphthoquinones has been synthesized and their reactions with amines, thiols, and halogen acids have been studied. The ultraviolet absorption maxima of many of these quinoncs are also tabulated.Canadian Journal of Chemistry, 46, 1859 (19GS) A number of 1,4-naphthoquinones were synthesized to determine their growth inhibitory activities against Stuphylococcus aureus (1) and also the relation of these activities to their partition coefficients in cyclohexane-water (2) and to their polarographic half-wave potentials (3). The inhibitory activities were independent of partition coefficients1 but exhibited a direct relationship to their polarographic half-wave potentials. The logarithms of the growth inhibitory activities for 1,4-naphthoquinones with unreactive groups at C-2 and C-3, when plotted against their half-wave potentials, gave two maxima, oile at -0.23 V and a less pronounced maximum at -0.36 V. The 1,4-naphthoquinones with a free position or a reactive group at C-2 or C-3 gave similar results when the logarithms of the growth inhibitory activities were plotted against the polarographic half-wave potentials of their C-2 or C-3 n-butylthio analogues. This was not true when their C-2 or C-3 amine analogues were used.These results (1) support the postulate (6) that 1,4-naphthoquinones or compounds such as 1,4,4a,9a-tetrahydroanthraquinone (7) which are readily converted to 1,4-naphthoquinones, function as bacterial growth inhibitors by functioning competitively in electron transport with the endogenous vitamin K or ubiquinone, thus decreasing the effectiveness of the latter as oxidative phosphorylating agents. For 1,4-naphthoquinones with unreactive groups at C-2 or C-3 to be effective growth inhibitors, this requires that their half-wave potentials lie between -0.163 to -0.307 V or -0.314 to -0.536 V (6) and that maximum effectiveiless should be intermediate between these limits. The 1,4-naphthoquinones with a free position or a reactive group at C-2 or C-3 may react with a bacterial protein-thiol or protein-amine prior to f~lnc-tioning as growth inhibitors, in which case the half-wave potentials of the derived 1,4-naphthoquinones must lie between these limits with maximum effectiveness intermediate between these limits. This paper reports the synthesis of a number of 1,4-naphthoquinones along with model 11-butylthio-, phenylthio-, n-butylamino-, and anilinoderivatives. The reactions leading to the model protein analogues were also used to classify substituents at C-2 and/or C-3, at least, in vitro, as reactive or unreactive and to demonstrate where these reactions did not follow the normal course.Anilino derivatives of the 1,4-naphthoquinone...

Fragmentation studies of synthetic 2‐acylamino‐1,4‐naphthoquinones by electrospray ionization mass spectrometry

“…1,4‐Naphthoquinones have also been shown to display biological activities, and they can act as antituberculosis,5 antimalarial,6, 7 antimicrobial8 and antitumor agents,9 as well as, molluscicide,10 larvicide,10 and herbicide11 agents. A considerable number of naphthoquinones containing amine groups in their structure or on the nitrogen atom have been associated with different biological activities 12, 13.…”

Electrochemical behavior of 1,2-dihydroxyanthraquinone dianion in aprotic solvents-DMSO and DMF: understanding the hydrogen bonding phenomena and protonation effect in biochemical systems

“…Also, quinone compounds have much importance in the field of biochemistry and medicinal chemistry [16] because compounds having quinone moiety play an important role in biological activities, these quinone containing compounds are also used as anti-tumor agents [17,18], anti-malarial [19], anti-bacterial [20], antineoplastic [21], anticoagulant [22], fungicides [23] and herbicides [24]. Since, the biological activity of quinoid compounds is due to the redox behavior of quinone system [9,16].…”

Anticancer Activity of 2‐Amino‐substituted‐1,4‐naphthoquinone Derivatives in Ovarian Cancer Cells

“…1 They are applied as anticancer, 2 antifungal, 3 antiviral, 4 antiplasmodial, 5 antibiotics, 6 and endothelial vasodilation agent. 7 Among the quinone derivatives, 2-amino-substituted-1,4-naphthoquinone derivatives show many interesting biological activities such as antitumour, 8 antimalarials, 9 antibacterials, 10 antituberculars, 11 and fungicides. 12 There are many chemotherapy drugs for the treatment of ovarian cancer such as platinum compounds, taxane compounds, altretamine, capecitabine, cyclophosphamide, etoposide, gemcitabine, ifosfamide, irinotecan, liposomal doxorubicin, melphalan, pemetrexed, topotecan, and vinorelbine.…”