Concise Synthesis of Some New Benzothiazole‐Based Heterocycles as Probable Anticancer and Antioxidant Agents

Abstract

Benzothiazole is the basic skeleton of multi‐target drugs with remarkable anticancer and antioxidant characteristics. In this research, new sets of benzothiazole derivatives carrying different pharmacophores and heterocyclic rings (e. g. 1,2,3‐triazole, pyrazole, thiazolidinone, thiophene, benzothiazole, 1,3‐dithiane, chromene, and pyrimidine) were efficiently synthesized through different synthetic routes from the newly synthesized ethyl 3‐(benzo[d]thiazol‐2‐ylamino)‐3‐oxopropanoate (1). These compounds were assessed in vitro as cytotoxic agents against two human cell lines, HCT‐116 (colon carcinoma) and WI‐38 (normal lung fibroblast) employing the MTT (3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide) assay, in which doxorubicin was used as a positive standard. Among the synthesized compounds, 1,2,3‐triazole 3 and pyrazoles 6 and 12 inhibited the growth of HCT‐116 cell line with high potency (IC50=7.54±0.7, 9.89±0.8, and 8.45±0.7 μM, respectively), along with low toxicity to normal cells, indicated their selectivity. Further, they were screened for their antioxidant performance using the ABTS (2,2′‐azino‐bis(3‐ethylbenzothiazoline‐6‐sulfonic acid)) bioassay and the results coincided with those of the cytotoxicity test, where the most powerful anticancer candidates displayed promising antioxidant activities with % inhibition 80.98 %, 84.12 %, and 88.82 %, respectively, comparable or superior to those of ascorbic acid (88.63 %).

A Novel PIFA/KOH Promoted Approach to Synthesize C2-arylacylated Benzothiazoles as Potential Drug Scaffolds

“…Benzothiazole skeletons exist as key building blocks in natural products, drugs and agrochemicals and exhibit potent and diverse biological activities [ 1 , 2 , 3 , 4 ]. The benzothiazole scaffold is considered to be one of the most important substructures for drug discovery due to its various biological effects, including anti-cancer, anti-oxidant, anti-inflammatory, anti-microbial, anti-fungal, anti-convulsant, and anti-viral activities [ 5 , 6 , 7 , 8 , 9 , 10 , 11 ]. Among them, C2-arylacylated benzothiazole derivatives have attracted considerable attention in recent years due to their great potential as new drug candidates.…”

Green Synthesis of 2‐Aminobenzothiazoles via Copper Catalysis under Microwave Irradiation

“…The beneficial pharmaceutical and biological characteristics of heterocyclic compounds could invite the attention of a large number of organic and medicinal chemists. Benzothiazole, having a thiazole ring fused to a phenyl ring, is a promising heterocyclic scaffold [1] . Numerous pharmaceuticals and natural products contain the 2‐aminobenzothiazole core in their structure (Figure 1).…”

“…Benzothiazole, having a thiazole ring fused to a phenyl ring, is a promising heterocyclic scaffold. [1] Numerous pharmaceuticals and natural products contain the 2-aminobenzothiazole core in their structure (Figure 1). [2] They are utilized for the synthesis of drugs used to treat diseases like tuberculosis, amyotrophic lateral sclerosis, epilepsy and so on.…”

Aminothiazole-Linked Metal Chelates: Synthesis, Density Functional Theory, and Antimicrobial Studies with Antioxidant Correlations

“…15 The extensive variety of the pharmacological actions of specific derivatives has shown that such compounds are also of undoubted importance. 16 Metalbased compounds are considered potential candidates for the replacement of traditionally employed organic drugs as several metal complexes of benzothiazoles have established their unique and potent behavior in medicine such as antimicrobial, 17 antileukemic, 18 anti-inflammatory, 19 and antidiabetic agents. 20 So, these things demand that there should be versatile changes in the structure and activity of such medicinally important compounds to cope with these challenges.…”

“…They have a range of therapeutic activities with a high degree of structural versatility that has been proved valuable in the quest for new therapeutic agents . The extensive variety of the pharmacological actions of specific derivatives has shown that such compounds are also of undoubted importance . Metal-based compounds are considered potential candidates for the replacement of traditionally employed organic drugs as several metal complexes of benzothiazoles have established their unique and potent behavior in medicine such as antimicrobial, antileukemic, anti-inflammatory, and antidiabetic agents .…”