In our efforts to discover novel multi‐target agents having better antitumor activities than celecoxib, 21 new aryl‐substituted pyrazole derivatives possessing cis‐diphenylethylene scaffold were mostly synthesized by a one‐pot approach to ethyl 1,4,5‐triaryl‐1H‐pyrazole‐3‐carboxylates via an improved Claisen condensation – Knorr reaction sequence. The cytotoxic effects of these compounds against three human cancer cell lines HT‐29, Hep‐G2, MCF‐7 as well as their inhibition of NO production were studied. Results showed that incorporation of the important pharmacophoric groups of two original molecules celecoxib and combretastatin A‐4 in a single molecule plays an important role in determining a better biological activities of the new coxib‐hybrided compounds.

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13 novel pyrazolo [4,3-c][2,1]benzothiazine 4,4-dioxide derivatives that mimic the pharmacophore of piroxicam as well as celecoxib were conveniently synthesized in a catalyst-free and atom-economical method in which an unconventional redox-neutral reaction of 2-nitrochalcones with elemental sulfur to straightforward access to 2,1-benzothiazine 2,2-dioxide core is the key step.Eight new pyrazolo[4,3-c][2,1]benzothiazine derivatives significantly inhibited NO production than the positive control. Besides that, most of the compounds exhibited weak cytotoxic activity suggesting a potent and selective antiinflammatory activity related to the antiproliferative activity of these novel compounds. Thus, incorporation of the pharmacophoric groups of the two above drugs in a single molecule plays an important role in determining a better antiinflammatory activity of the new compounds.

In this report, we have described the concise elaboration of 12 novel 5‐thiourea‐4‐aza‐2,3‐didehydropodophyllotoxin‐derivatives by the unconventional multicomponent reaction was based on a catalyst‐free and atom‐economical method. The synthetic approach features methodology using sulfur element in thiourea synthesis. Cytotoxicity of compounds was evaluated for their inhibition rate of cell growth against two human tumor cell lines (MCF‐7 and Hep‐G2). Some new 5‐thiourea‐4‐aza‐2,3‐didehydropodophyllotoxin such as 15a, 15d, 15l exhibit very good cytotoxicity and much more stronger than their precursor 5 amino‐4‐aza‐2,3‐didehydropodophyllotoxin. The number and chemical characters of the Cα substituents of the thiourea group may have a decisive role in the activity of the molecules. Docking studies of the tested molecules proved that compound 15a, 15d, 15l exhibit high binding affinity toward human topoisomerase II beta in compare to the reference inhibitor, etoposide. Further dock pose analysis sugessted these molecules as potential inhibitors‐based on their key interaction with residues within binding site of the protein.