Abstract:
Background: Sulfonamides are an important class of drugs and possess various biological
properties. Tertiary sulfonamides with di-(2-picolyl)amine have been proposed as a new way
to conjugate biological targets of interest.
Objective: The objective was to synthesize novel di-(2-picolyl)amine derivatized sulfonamide
ligands towards the discovery of novel drug leads.
Method: Two novel ligands; N(SO2imidazole)dpa (L1) and N(SO2methylimidazole)dpa (L2)
were synthesized and characterized by 1HNMR, FT-IR, UV-Vis and fluorescence
spectroscopic methods. Single crystal X-ray diffraction was carried out for L1. Biological
target prediction was carried out using ‘SwissTargetPrediction’ and ‘SwissADME’ servers.
Molecular docking studies were carried out using AutoDock Vina wizard in the PyRx 0.9.4
software.
Results: Structural data for L1 confirms that the S-N bond length (1.6385 Å) is within the
accepted range of sulfonamide bond length. In 1HNMR spectra, peaks related to the aromatic
protons of L1 and L2 were identified in the region of 7.0-8.4 ppm and a singlet peak was
observed at 4.50 ppm and 4.65 ppm, respectively for methylene protons. High energy
absorption bands in the region of 200-300 nm in UV-Vis spectra indicate intra-ligand ᴫ-ԯ* and
n-ᴫ* transitions. Both ligands display high fluorescence intensities in the visible range. In silico
analysis of drug-likeness shows that both ligands comply with the Lipinski rule of five. It is
predicted that serine-threonine protein kinase is a potential target for L1 with a calculated
binding affinity of -6.7 kcal/mol. Furthermore, L1 was predicted to bind with Aromatase and
Glucosamine-6-phosphate synthase with binding affinities of -6.6 kcal/mol and -8.2 kcal/mol
showing potential to be anti-cancer and anti-microbial drug leads, respectively. GABA-A
receptor was a potential target for L2 where it can be analyzed as a sedative and anxiolytic drug
lead.
Conclusion: Two new ligands have been synthesized and characterized and their drug-likeness
indicate that they can be investigated towards biological applications.
