Background:
Many synthetic procedures were reported till date to prepare pyrazoline
derivatives. Some have published pyrazolines from different chalcone derivatives in the literature.
Objective:
A series of new pyrazolines containing novel 2,5-dichloro-3-acetylthiophene chalcone
moiety (PZT1-PZT20) have been synthesized, characterized by 1HNMR and 13CNMR and evaluated
for them in vitro antitubercular activity against M. tuberculosis H37Rv strain and in vitro
anticancer activity against DU-145 prostate cancer cell lines and all compounds were also
screened for molecular docking studies against specific targeted protein domains.
Methods:
All compounds were screened for potential activity against Mycobacterium tuberculosis
H37Rv (MTB) strain and anticancer activity against DU-149 prostate cancer cell lines using MTT
cytotoxicity assay.
Results:
Among the series, compound PZT5 with 2”, 4”-dichlorophenyl group at 5-position on the
pyrazoline ring exhibited the most potent antitubercular activity (MIC=1.60 µg/mL) and compounds
PZT2, PZT9, PZT11, PZT15, and PZT20 showed similar antitubercular activity against
standard pyrazinamide (MIC=3.12 µg/mL) by broth dilution assay. PZT15 and PZT17 with 4”-
pyridinyl and 2”-pyrrolyl groups on pyrazoline ring were found to exhibit better anticancer activity
against DU-149 prostate cancer cell lines with IC50 values of 2.0±0.2 µg/mL and 6.0±0.3
µg/mL respectively by MTT assay. The preliminary structure-activity relationship has been summarized.
The molecular docking studies with crystalline structures of enoyl acyl carrier protein
reductase InhA interaction with target protein (2NSD; PDB and 3FNG; PDB) of Mycobacterium
tuberculosis H37Rv (MTB) strain have also exhibited good ligand interaction and binding affinity.
Ligand interaction and binding affinity were estimated using crystal structures of both types of
enoyl acyl carrier protein reductase InhA (3FNG.pdb) and found to be much higher (-16.70 to -
19.20 kcal/mol) compared with pyrazinamide (-10.70 kcal/mol) as a standard target molecule.
Whereas the binding affinities of six active compounds with crystal structure of other type of
enoyl acyl carrier protein reductase InhA (2NSD.pdb) were much similar and higher (-9.30 to -
11.20 kcal/mole) than pyrazinamide (-11.10 kcal/mole).
Conclusion:
These new pyrazolines would be promising potent inhibitors of drug sensitive and
drug resistant Mycobacterium tuberculosis strain and potential anticancer agents against prostate
cancer and other prototypes of cancers.
DNA polymerase III a subunit from Mycobacterium tuberculosis H37Rv: Homology modeling and molecular docking of its inhibitor
