Sydnones have been a novel class of mesoionic compound due to versatility of their applications in
various fields. Sydnone derivative have seen as an interesting structure grouped in the heterocyclic
community, which is having regions of both positive and negative charges linked with a
poly-heteroatomic system. This structural characteristic allows them to cross biological membranes and
interact with biomolecules. Four sydnones namely 3-(4-decyloxybiphenyl-4′-yl) sydnone (MC-176),
3-(4-octyloxy-2,3-difluorobiphenyl-4′-yl) sydnone (MC-192), 3-(4-biphenyl-4′-yl) sydnone (MC-450)
and 3-(4-butylbiphenyl-4′-yl) sydnone (MC-456) were evaluated for biophysical interactions between
DNA and sydnones and antiproliferative activity. The UV-visible spectroscopic study indicates
interaction between sydnone and dsDNA with a slight red and hypochromic shift in absorption spectra,
which shows the intercalation mode of binding. The binding constant of DNA-Sydnone complexes
were in the range from 1.4 × 104 M–1 to 7.1 × 104 M–1 for different sydnone compounds (MC-176,
MC-192, MC-450, MC-456). FTIR spectra indicated that sydnone interaction with DNA occurs through
base pairs and the phosphate backbone of the DNA. The cytotoxic and apoptotic effects of a sydnone
derivatives on human cervical cancer (HeLa) and breast tumor (BT) 474 cancer cell lines were
determined. The compounds possess antiproliferative activity in a concentration-dependent mode.
The changes of morphological characteristic of cancer cells were determined by fluorescent staining
techniques indicate the apoptotic cell death. The molecular docking studies of sydnone compounds
with caspase 3 and EGF-TK showed better interactions (according to docking score) along with
commercially available breast cancer drug molecule anastrozole. The docking score of sydnone molecules
(MC-456, MC-450, MC-192 and MC-176) with EGF-TK enzyme were -6.44, -6.42, -5.46 and -4.53,
respectively. The binding energy of anastrozole with EGF-TK was -6.41. As well Caspase 3 inhibition
with sydnone compounds MC-456, MC-450, MC-192 and MC-176 were -6.09, -6.48, -5 and -3.49,
respectively. The binding energy of anastrozole with caspase 3 was -6.24. All sydnone compounds
were studied for ADME toxicity studies along with Lipinski rule of five to assess their drug likeness
properties by in silico approach. MC-450 found to have good ADMET (absorption, distribution,
metabolism, excretion and toxicology) properties among all the sydnone compounds. Thus, the present
work indicates that these sydnone compounds would be a well prospective in developing anticancer
medicines.
Synthesis and crystal structure of new monometallic Ni(ii) and Co(ii) complexes with an asymmetrical aroylhydrazone: effects of the complexes on DNA/protein binding property, molecular docking, and in vitro anticancer activity
