Molecular association of 2-(n-alkylamino)-1,4-naphthoquinone derivatives: Electrochemical, DFT studies and antiproliferative activity against leukemia cell lines

• Published in: Journal of molecular structure 2016-12, Vol.1125, p.272-281
• Main Authors: Patil, Rishikesh, Bhand, Sujit, Konkimalla, V. Badireenath, Banerjee, Priyabrata, Ugale, Bharat, Chadar, Dattatray, Saha, Sourav Kr, Praharaj, Prakash Priyadarshi, Nagaraja, C.M., Chakrovarty, Debamitra, Salunke-Gawali, Sunita
• Format: Article
• Language: English
• Subjects: Aminonaphthoquinone; Antiproliferative activity; Hydrogen bonding; Redox potential
• ISSN: 0022-2860; 1872-8014
• DOI: 10.1016/j.molstruc.2016.06.075

Molecular structures and their molecular association of 2-(n-alkylamino)-1,4-naphthoquinone, viz., LH-3; propyl, LH-4; butyl and LH-8; octyl derivatives were studied by single crystal X-ray diffraction studies. Synthesis and characterization of 2-octylamino-1,4-naphthoquinone; LH-8 was discussed. The molecule of LH-3 crystallizes in orthorhombic space group P21/c, while the LH-4 and LH-8 molecule crystallizes in triclinic space group P-1. LH-3, LH-4 and LH-8 showed intermolecular N-H⋯O and C-H⋯O interactions, LH-3 showed unique C(3)-H(3)⋯O(1) interaction. Interchain π-π stacking, slipped π-π stacking and C⋯O close contacts was respectively observed in LH-3, LH-4 and LH-8. Electrochemical studies were performed on first eight members of homologous series of 2-(n-alkylamino)-1,4-naphthoquinone (LH-1 to LH-8) by cyclic voltammetry. Naphthoquinone to naphthosemiquinone reversible redox couple was observed in all compounds ∼ E1/2 = −0.657 ± 0.05 V. HOMO-LUMO band gap was determined for the neutral form as well as the monoanionic radical form viz. naphthosemiquinone form of selected derivatives by DFT studies. It has been observed that the electron density is delocalized in the naphthoquinone ring in both neutral as well as one electron reduced form of compounds. Antiproliferative activity of LH-1 to LH-8 was evaluated against two cancer cell lines, THP1(acute monocytic leukemia) and K562(human immortalized myelogenous leukemia cell line) cells. It was observed that, in THP1 cells, compounds LH-2 and LH-3 are very active while LH-1, LH-4 and LH-6 were moderately active and LH-5, LH-7 and LH-8 were totally inactive. Contrastingly, in K562 cells all of the compounds were moderately active. [Display omitted] •Molecular association of n-alkylamino-1,4-naphthoquinones were studied.•Crystal structures of propyl, butyl and octyl derivatives are presented.•Redox potentials are determined by cyclic voltammetry.•HOMO-LUMO band gap determined by DFT studies.•Antiproliferative activity studied on leukemia cell line.