Pass and Swiss ADME collaborated in silico docking approach to the synthesis of certain pyrazoline spacer compounds for dihydrofolate reductase inhibition and antimalarial activity

New series of pyrazoline spacer compounds were prepared by the reaction between benzimidazole chalcones and (2-methyl-5-nitro-imidazole-1-yl)-acetic acid hydrazide by the sensible use of Michael addition. The building blocks used for the synthesis of pyrazoline derivatives were opted by using virtual screening by molinspiration search engine. The hypothetically resulted pyrazoline spacer compounds from this list are checked for their reliability on other in silico drug designing online web services like PASS online bioactivity, Swiss ADME predictor. The docking study on final four pyrazoline compounds was carried out using Accelrys Discovery Studio 3.5. These synthesized compounds were, later, characterized with the help of UV, IR, mass and 1H NMR techniques. These compounds were further screened for their in vitro antimalarial effect. The PASS, Swiss ADME assisted docking approach and the use of combo heterocyclic ring with pyrazoline scaffold were found to be beneficial to derive and synthesize effective antimalarial agents in the present study. Video Clip of Methodology: 6 min 20 sec:   Full Screen   Alternat

Microwave assisted synthesis of novel pyrazolone derivatives attached to a pyrimidine moiety and evaluation of their anti-inflammatory, analgesic and antipyretic activities

AbstractIn the present research work, the motto was to develop new chemical entities as potential anti-inflammatory, analgesic and antipyretic agents. Various 4-(2-amino-6-(substituted)pyrimidin-4-yl)-3-methyl-1-(substituted)-1H-pyrazol-5(4H)-one derivatives (5a–5j) and their Schiff bases (6a–6j) were synthesized. The newly synthesized compounds were characterized by TLC and spectral data. The compounds containing pyrazolone and amino pyrimidine as basic moieties (5a–5j), were screened for their anti-inflammatory, analgesic and antipyretic activities, compounds 5a, 5c–5f, 5h exhibited activities nearly similar to the standard. The pharmacological studies reveal that the presence of 4-hydroxy, 4-methoxy, 4-(N,N-dimethylamino) or 2-hydroxy groups on phenyl ring at C6 of amino pyrimidine exhibits anti-inflammatory, analgesic and antipyretic activities nearly similar to the standard and substitutions like 4-chloro, 2-nitro, 3-nitro or 4-nitro on same phenyl ring lead to a decrease in activities