Molecular structures and biological evaluation of 2-chloro-3-(n-alkylamino)-1,4-napthoquinone derivatives as potent antifungal agents

•2-chloro-3-(n-alkylamino)-1,4-naphthoquinones are synthesized and characterized.•Single crystal X-ray structures reveal molecular association by hydrogen bondings.•Molecular associations of aminonaphthoquinones are revealed by cyclic voltammetry.•Antifungal activity is studied against C. tropicalis, C. albicans and C. herbarum.•Methyl derivative shows promising antifungal activity.

Derivatives of 2-chloro-3-(n-alkylamino)-1,4-naphthoquinone {n-alkyl: methyl; L-1, ethyl; L-2, propyl; L-3 and butyl; L-4} have been synthesized and characterized by elemental analysis, FT-IR, 1H NMR, UV–visible spectroscopy, LC-MS and single crystal X-ray diffraction studies. Antifungal activity of L-1 to L-4 has been evaluated against Candida tropicalis, Candida albicans and Cladosporium herbarum. The intramolecular hydrogen bonding affects the N–H vibrational frequency in L-2 (3273 cm−1). The single crystal X-ray structure reveal that L-1 and L-3 crystallizes in triclinic P-1, whereas L-2 crystallizes in orthorhombic Pca21 space group. An extensive intra and intermolecular hydrogen bonding interactions were observed in L-1 to L-3 which leads to molecular association. Intramolecular N–H⋯O hydrogen bonding were observed in L-1 to L-3. Moreover π–π stacking interactions were observed between the quinonoid rings of L-1 and L-3, however no such interactions were observed in L-2. An electrochemical study showed molecular association of L-1 to L-4 in DMSO solution. Compounds L-1 to L-4 were found to be potent antifungal agents against all the three strains, especially against C. tropicalis. Amongst these promising antifungal candidates, L-1 showed better activity compared to the clinically administered antifungal drug Amphotericin B and Nitrofurantoin with MIC = 1.25 μg ml−1 and MIC = 0.025 μg ml−1 respectively against C. albicans. Structure and activity relationship (SAR) study suggest a Log P value of ∼2.0 and the cyclic voltammetry studies reveals additional chemical processes for L-1, which exhibits maximum activity against all fungal strains.