Design, synthesis, biological evaluation and molecular docking study based on novel fused pyrazolothiazole scaffold
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ORIGINAL PAPER
Design, synthesis, biological evaluation and molecular docking study based on novel fused pyrazolothiazole scaffold Hala F. Rizk1 · Mohamed A. El‑Borai1 · Ahmed Ragab2 · Seham A. Ibrahim1 Received: 26 February 2020 / Accepted: 24 April 2020 © Iranian Chemical Society 2020
Abstract 3-(Pyridin-3-yl)-1-p-tolyl-1H-pyrazolo[3,4-d]thiazol-5-amine was used as a key synthon for a one-pot two- and threecomponent synthesis of new fused heterocyclic moieties as pyrazolo[3,4-d]thiazole derivatives containing new fused ring pyrimidines or imidazoles. The compounds were synthesized by using microwave irradiation as an eco-friendly technique besides the conventional heating. All the newly synthesized compounds were characterized on the basis of their physical, spectral and analytical data. Most of the synthesized compounds were evaluated for their in vitro antimicrobial potentialities and antioxidant activities, and the most promising compounds were selected to determine antitumor activity. Molecular docking was performed inside the active site of cathepsin D, and target compounds 5a–c had a good binding energy of − 16.87 to − 11.64 kcal/mol compared to that of original ligand of − 16.02 kcal/mol with different binding interactions, thereby suggesting that these compounds may possibly act as cathepsin D inhibitors and thus may participate in anticancer activity. Keywords Pyrazolothiazole · Microwave irradiation · Antimicrobial potentialities · Antioxidant activity · Antitumor activity · Molecular docking
Introduction Pyrazoles and their derivatives have a broad spectrum of biological activities such as antimicrobial [1], anti-inflammatory [2], antifungal [3], antiviral [4], analgesic, antitumor, cytotoxic and antipyretic activities and obesity [5–7]. Celecoxib, sulfaphenazole, CDPPB, Lonazolac-Ca, mepiprazole and rimonabant are some of the pyrazole-based drugs available today in the market [8]. Thiazoles are privileged motifs that are encountered in many naturally occurring bioactive and pharmaceutical compounds with an indication in a number of therapeutic areas including antimicrobial [1, 9, 10], analgesic [11], anti-inflammatory [12], anticonvulsant [13], anticancer [14], anti-tubercular [15], anthelmintic [16] and antidepressant activities [17]. In an attempt to provide synergistic cytotoxicity activity, these two moieties have been combined and the resulting * Hala F. Rizk [email protected] 1
Department of Chemistry, Faculty of Science, Tanta University, Tanta 31527, Egypt
Department of Chemistry, Faculty of Science (Boys), Al-Azhar University, Nasr City, Cairo 11651, Egypt
2
novel pyrazolothiazole analogs, which play a vital role in the field of medicinal chemistry, are considered as an important pharmacophore and exhibit outstanding biological activities [18–21] as protein kinase modulators for treating cancer and other diseases [22–24]. These compounds were synthesized from 3-(pyridin-3-yl)-1-p-tolyl-1H-pyrazolo[3,4-d]thiazol5-amine as a starting compound, and its reaction with a variety
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