Synthesis, crystal structure, molecular dynamics, docking and in-vitro studies of cyclododecanonethiosemicarbazone, a promising anti tuberculosis agent

Abstract

Cyclododecanonethiosemicarbazone (CDT), crystallises in triclinic crystal system in spacegroup P-1 having unit cell parameters as a = 5.6152(2)Å, b = 8.3747(4) Å, c = 16.1901(7) Å, α = 91.186(2)°, β = 90.880(2)° and γ = 108.014(2)°, V = 723.68(5) Å3 and Z = 2.The macrocyclic ring structure shows close resemblance to the most stable conformation for a 12 membered aliphatic cyclic ketone, where three C-C bonds are present on each side of the heavy atom framework's square structure. Existence as thione form of the compound is confirmed by IR, NMR and Crystallographic data. There is extensive electron delocalisation along its thiosemicarbazone moiety. A number of short term interactions, including three intermolecular H-bonding interactions involving each S, forms infinite interlinked chains of molecules along a axis. Results of anti tuberculosis activity studies reveal that minimum inhibitory concentration (MIC) of CDT is 800 µg/mL for the test organism Mycobacterium smegmatis. Hirshfeld surface analysis, docking and molecular dynamics studies suggest stable protein –ligand binding with the related 1TEX protein.

Keywords

• Macrocyclic ring structure
• Square configuration
• Thiosemicarbazone
• Cyclododecanone
• Hirsfeld studies
• Anti-tuberculosis agent