Synthesis, in silico and in vitro Evaluation of 1, 3, 4-Thiadiazole Derivatives Fused with Biphenyl Compound

Background

1,3,4-thiadiazole nucleus is a flexible nucleus. There are numerous biological activities showed by this nucleus. Anticancer, anthelmintic, antimicrobial, anti-inflammatory, antioxidant; anti-HIV, anti- tubercular and anti-carbonic anhydrase are a few activities showed by 1,3,4-thiadiazole derivatives. This project study aimed to investigate the anthelmintic and in silico anticancer activity of derivatives of 1,3,4-thiadiazole.

Materials and Methods

The UV visible spectrophotometer (Shimadzu UV-1900) has been used to determine λ_max of the synthesized molecules. The FT-IR (Bruker Alpha-II) spectrometer was used for IR spectra (4000-400 cm^-1) via the KBr disc method. Proton (1H) and Carbon-13 (13C) NMR spectra were recorded in CDCl3 or (D6) DMSO at 300-500 MHz and 101-125 MHz, respectively, using the Bruker AV-III 400 spectrometer (Germany). High-Resolution Mass Spectra (HRMS) were obtained using the Xevo G2-XS QT of Mass Spectrometer (USA) with positive ESI mode at 70 eV.

Results

The bonding energy for compounds 1, 2 and 3 were all in the range -42.929 to -48.909 kcal/mol. Results of the docking study shows interactions of compound 3 with the neighboring residues and showing significant anticancer activity. The presence of o-nitro, m-nitro and p-hydroxy groups makes compounds 1 (105.77%), 2 (131.67%) and 3 (155.54%) more potent and nearly equal in terms of inhibition percentage when compared to standard ascorbic acid. Compound-1 [5-([1,1’-biphenyl]-4-yl)- N -(2-nitrobenzylidene)- 1,3,4-thiadiazol-2-amine] showed significant anthelmintic activity.

Conclusion

The biological profiles of these new generations of thiadiazoles would represent a fruitful matrix for further development of better medicinal agents.