The α-glucosidase is a validated target to develop drugs for treating type 2 diabetes mellitus. The existing α-glucosidase inhibitors have certain shortcomings related to side effects and route of synthesis. Accordingly, it is inevitable to develop new chemical templates as α-glucosidase inhibitors. Pyrazole derivatives have a special place in medicinal chemistry because of various biological activities. Recently, pyrazole-based heterocyclic compounds have emerged as a promising scaffold to develop α-glucosidase inhibitors. This study focuses on the recently reported pyrazole-based α-glucosidase inhibitors, including their biological activity (in vivo, in vitro, and in silico), structure-activity relationship, and ways of synthesis. The literature revealed the development of several promising pyrazole-based α-glucosidase inhibitors and new synthetic routes for their preparation. The encouraging α-glucosidase inhibitory results of the pyrazole-based heterocyclic compounds make them an attractive target for further research. The authors also foresee the arrival of the pyrazole-based α-glucosidase inhibitors in clinical practice.

A series of newer benzothiazolotriazine derivatives (4a-k) was designed, synthesized, and characterized as anticonvulsant agents against the two classically used MES and scPTZ animal models. The synthesized derivatives were tested in vivo in both the animal models, followed by a neurotoxicity study by the rotarod method. Compound 3,5]triazine was found most promising among the series in both the animal models, with no neurotoxicity. From this it may be confirmed that the presence of a methoxy (OCH 3 ) group at the lipophilic aryl ring was showing high anticonvulsant potency. In the molecular modeling study, compound 4e (docking score = −8.70) showed important hydrogen bond interaction with the amino acids LYS 329, SER 137, GLY 136 and π-π interactions with PHE 189 at the active site of GABA-AT. These derivatives can be further explored for the development of newer/novel anticonvulsant agents. K E Y W O R D S

Background: The epidermal growth factor receptor (known as EGFR) induces cell differentiation and proliferation upon activation through the binding of its ligands. Since EGFR is thought to be involved in the development of cancer, identification of new target inhibitor is the most viable approach which recently gained momentum as a potential anticancer therapy. Objective: To assess various pyrazole linked pyrazoline derivatives with carbothioamide for EGFR kinase inhibitory as well as anti-proliferative activity against human cancer cell lines viz. A549 (non-small cell lung tumour), MCF-7 (breast cancer cell line), SiHa (cancerous tissues of the cervix uteri) and HCT-116 (colon cancer cell line). Methods: In vitro EGFR kinase assay, In vitro MTT assay, Lactate dehydrogenase release, Nuclear staining (DAPI) and Flow cytometry cell analysis. Results: Compounds 6h and 6j inhibit EGFR kinase at concentrations of 1.66 µM and 1.9 µM respectively. Furthermore, the compounds 6h and 6j showed the most potent anti-proliferative results against the A549 KRAS mutation cell line (IC50 = 9.3 & 10.2 µM). Through DAPI staining and phase contrast microscopy, it was established that compounds 6h and 6j also induced apoptotic activity in A549 cells. This activity was further confirmed by FACS using Annexin-V-FITC & propidium iodide (PI) labelling. Molecular docking studies performed on 6h and 6j suggested that the compounds can bind to the hinge region of ATP binding site of EGFR tyrosine kinase in a similar pose as that of the standard drug gefitinib. Conclusion: The potential anticancer activity of the compounds 6h and 6j was confirmed and needs further exploration in cancer cell lines of different tissue origin and signalling pathways as well as on animal model of cancer development.

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