Design, Synthesis and Evaluation of Novel Benzimidazoles, Benzothiazoles and Benzofurans Incorporating Pyrazole Moiety as Antiangiogenic Agents

Abstract

Novel benzimidazoles, benzothiazoles and benzofurans incorporating pyrazole moiety have been synthesized and screened for their antiangogenic activities, by testing their ability to inhibit human umbilical vein endothelial cell (HUVEC) proliferation, cord formation and migration in response to chemoattractant. 3 compounds 19, 23 and 26 showed antiangiogenic activities at non-cytotoxic concentrations. Compound 19 was the most active with chemotaxis activity data nearly comparable to that of the positive control, TNP-470. Compound 42 showed a significant cytotoxic effect on the tested cancer cell lines and less antiangiogenesis activity compared to compounds 19, 23 and 26. All the tested compounds, in contrary to TNP-470, interfered with the migratory function of HUVECs in response to vascular endothelial growth factor rather than the endothelial cells proliferation or cord formation. Moreover, a docked pose of compounds 19 and 26 was obtained bound to kinase insert domain receptor using Molecular Operating Environment module.

Molecular Hybrids Integrated with Benzimidazole and Pyrazole Structural Motifs: Design, Synthesis, Biological Evaluation, and Molecular Docking Studies

“…Two of the molecular hybrids, 6e and 6i were reported as potential therapeutics for human umbilical vein endothelial cell (HUVEC) proliferation. 61 According to the report, HUVEC was used as an antiangiogenesis cell model. However, as our group has been working on the development of a diverse range of heterocyclic molecular hybrids as anticancer agents against pancreatic cancer in the recent years, our aim in this study is to focus on the effects on pancreatic cancer cells.…”

“…Two of the molecular hybrids, 6e and 6i were reported as potential therapeutics for human umbilical vein endothelial cell (HUVEC) proliferation . According to the report, HUVEC was used as an antiangiogenesis cell model.…”

Small Peptide Conjugates of Benzothiazole‐2‐Carboxylic Acids Targeting DprE1 Against Tuberculosis

“…TCA1 analogues bearing benzothiazole war heads were proved to be noncovalent inhibitors of DprE1. [2,[24][25][26][27][28] Furthermore, in the last few decades, several peptides have been identified as promising drug candidates for M.tb (Figure 3). They have demonstrated potential anti-tubercular activities alone as well as in combination with pre-existing drugs.…”

“…Moreover, most of the newly explored non‐covalent DprE1 inhibitors contain the benzothiazole nucleus, which has already been established as a potent pharmacophore well‐known for other important pharmacological properties including anti‐cancer, anti‐malarial, anti‐diabetic, anti‐microbial, anti‐convulsant, anti‐HIV, and anti‐leishmanial activities. TCA1 analogues bearing benzothiazole war heads were proved to be non‐covalent inhibitors of DprE1 [2,24–28] …”

Screening and Molecular Docking of Novel Benzothiazole Derivatives as Potential Antimicrobial Agents

“…The benzothiazole nucleus, with a variety of modifications, has demonstrated a wide range of pharmacological properties including antimicrobial [5], anti-HIV [6], anthelmintic [7], antidiabetic [8], anticonvulsant [9], larvicidal [10], antimalarial [11], and anticancer activities [12]. In addition, the potential antimicrobial activity of benzothiazole derivatives was previously illustrated [13][14][15][16][17].…”