Synthesis, characterization, and theoretical studies of (E)-t-butyl-2((E)-2-methyl-3-phenylallylidene) hydrazine carboxylate and (E)-t-butyl-2-((E)-3-phenylallylidene) hydrazine carboxylates as a possible Mcl-1 antagonists

Refluxing t-butyl carbazate with the corresponding aldehyde in ethanol yielded (E)-tert-butyl 2-((E)-2-methyl-3-phenylallylidene)hydrazinecarboxylate (1) and (E)-t-butyl-2-((E)-3-phenylall ylidene)hydrazine carboxylate (2) in appreciable amounts. The products were identified using spectral data analysis. To confirm the trans-nature of the double bond in the synthesized compound 1, single crystal X-ray analysis was carried out. The trans-nature of double bond in compound 2, which could not be crystallized, was however deduced from the vicinal coupling constant of the two protons involved in the double bond. Single crystal X-ray study unfurled that compound 1 crystallizes in a monoclinic system with P2(1)/c space group. Theoretical calculations of both the compounds was carried out at DET/B3LYP/6-311G (d, p) level of theory. Theoretically obtained parameters demonstrated good compliance with the experimentally obtained data for compound 1. Molecular Electrostatic Potential Surface (MEPS) and Frontier Molecular Orbital (FMO) analysis were performed for both the compounds. Calculation of HOMO-LUMO energy gap and various other related parameters depicted a similar reactivity behaviour of both the compounds. To unravel the biological target of the compounds, Online Pass Prediction divulged that compounds, 1 and 2 are moderately potent against Mcl-1 enzyme, with Pa value of 0.82 and 0.61 respectively. Molecular docking of 1 and 2 against Mcl-1 protein conferred binding free energy of -6.26 and -3.11 kcal/mol respectively indicating moderate binding efficiency of the compounds. (C) 2018 Elsevier B.V. All rights reserved.