Novel Thiophene Thioglycosides Substituted with the Benzothiazole Moiety: Synthesis, Characterization, Antiviral and Anticancer Evaluations, and NS3/4A and USP7 Enzyme Inhibitions

Abstract

Novel derivatives of benzothiazole-2-thiophene Sglycoside were synthesized and tested for their antiviral and anticancer potency and NS3/4A and USP7 enzyme inhibitions. The ring system was formed by first synthesizing new derivatives of 5-mercaptothiophene substituted with the benzothiazole moiety, followed by coupling with various halo sugar derivatives. New compounds were tested in vitro for the cytotoxic effect on five types of normal cell lines and for antiviral activity using a plaque reduction assay against CBV4, HSV-1, HCVcc genotype 4 viruses, HAV HM 175, and HAdV7. Notably, three compounds demonstrated substantial IC 50 , CC 50 , and SI values against HSV-1 with a viral reduction of 80% or more. Two substances have demonstrated a reduction of more than 50% in CBV4 and HCVcc viruses. The effectiveness of the compounds against HSV-1 and HCVcc was tested for their capability to inhibit NS3/4A protease and USP7 enzyme. Additionally, a panel of 60 human cancer cells was used to investigate the ability of the newly synthesized compounds to inhibit the in vitro tumor growth. The results revealed that two compounds, 6a and 6c, have an inhibitory effect on most cancer types, whereas 6d and 6f inhibited only three and two cell lines, respectively.

Crystal structure of N-[3-(benzo[d]thiazol-2-yl)-6-bromo-2H-chromen-2-ylidene]-4-methylbenzenamine

“…Coumarin (IUPAC name 2H-chromen-2-one) is a natural product and flavouring agent. Recently, a series of novel benzothiazolyl-coumarin hybrids have been synthesized as potential biological agents and efficient emitting materials (Azzam et al, 2021(Azzam et al, , 2022aWu et al, 2011). We have previously prepared 3-(benzo[d]oxazol, -imidazole, -thiazol-2-yl)-2H-chromen-2imine and their corresponding coumarin analogues 3-(benzo [d]oxazol-, -imidazol, -thiazol-2-yl)-2H-chromen-2one, through the reaction of salicylaldehyde with 2-cyanomethyl-benzoxazole, -benzimidazole, and -benzothiazole, respectively (Elgemeie, 1989).…”

In the pursuit of novel therapeutic agents: synthesis, anticancer evaluation, and physicochemical insights of novel pyrimidine-based 2-aminobenzothiazole derivatives

“…20 In our previous investigations, we undertook the design and synthesis of a series of innovative benzothiazole derivatives in conjunction with pyrimidine, 21 pyridine, 22,23 purine analogues, 24 or thiophene ring. 25 These compounds were evaluated for their antimicrobial, antiviral, and/or anticancer activities. 26 Recognizing the key role of 2-aminobenzothiazole as a promising anticancer agent, our exploration was encouraged to create new derivatives of 2-aminobenzothiazole, specically in collaboration with the pyrimidine ring.…”

Novel Fluorescent Benzothiazolyl-Coumarin Hybrids as Anti-SARS-COVID-2 Agents Supported by Molecular Docking Studies: Design, Synthesis, X-ray Crystal Structures, DFT, and TD-DFT/PCM Calculations

“…Heterocyclic molecule-based benzothiazole derivatives exhibit strong fluorescence and luminescence in the solid state and in solutions . Recently, we synthesized novel heterocyclic derivatives substituted with a benzothiazole moiety that showed important fluorescence and significant biological activities. − Among the compounds with valuable optical properties and biological activities are the substituted coumarins containing benzothiazole residue . In this regard, emerging more competent methods for synthesizing this structure for a useful pathway to motivated chemical collections of coumarins containing benzothiazole residue would be extremely required.…”