Synthetic and anti-cancer activity aspects of 1, 3, 4-thiadiazole containing bioactive molecules: A concise review

Obakachi, Vincent A.; Kushwaha, Babita; Kushwaha, Narva Deshwar; Mokoena, Sithabile; Ganai, Ab Majeed; Pathan, Tabasum Khan; Zyl, Werner E. van; Karpoormath, Rajshekhar

doi:10.1080/17415993.2021.1963441

Cited by 15 publications

(8 citation statements)

References 61 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…1,3,4-thiadiazole is a five-membered heterocyclic compound with three heteroatoms, which exists as a structural subunit in a number of bioactive compounds [31][32][33][34][35]. Molecules possessing thiadiazole fragment have shown anticancer [36][37][38][39], antimicrobial [40,41], antiepileptic [42], and many other properties. Among the variety of clinically used representatives, the antibiotics cefazolin and azamulin are shown on Figure 1.…”

Section: Introductionmentioning

confidence: 99%

4-Methyl-7-((2-((5-methyl-1,3,4-thiadiazol-2-yl)thio)ethyl)thio)-coumarin

Kurteva

Rusew

Shivachev

2022

Molbank

View full text Add to dashboard Cite

show abstract

Section: Introductionmentioning

confidence: 99%

4-Methyl-7-((2-((5-methyl-1,3,4-thiadiazol-2-yl)thio)ethyl)thio)-coumarin

Kurteva

Rusew

Shivachev

2022

Molbank

View full text Add to dashboard Cite

show abstract

“…In STC4-S2, we included a benzothiazole-2-sulfonate (BTS) ester, which takes advantage of an electron-withdrawing heteroaromatic group and was employed successfully in coumarin- and fluorescein-based sensors . In addition, we synthesized prochelators STC4-S3 and STC4-S4 carrying the 1,3,4-thiadiazole moiety, an important heteroaromatic motif found in a broad variety of pharmaceuticals and agrochemicals. − Its favorable solubility and stability profiles in aqueous solutions, as well as its electron-deficient nature, make the 1,3,4-thiadiazole ring an attractive moiety for the design of thiol-reactive sulfonate ester prodrugs. Furthermore, we reasoned that substitution at the 5 position (i.e., Me vs Ph in STC4-S3 and STC4-S4, respectively) would allow tuning of the electrophilic properties.…”

Section: Resultsmentioning

confidence: 99%

Thiol-Reactive Arylsulfonate Masks for Phenolate Donors in Antiproliferative Iron Prochelators

Sung

Tomat

2022

Inorg. Chem.

View full text Add to dashboard Cite

Tridentate thiosemicarbazones, among several families of iron chelators, have shown promising results in anticancer drug discovery because they target the increased need for iron that characterizes malignant cells. Prochelation strategies, in which the chelator is released under specific conditions, have the potential to avoid off-target metal binding (for instance, in the bloodstream) and minimize unwanted side effects. We report a prochelation approach that employs arylsulfonate esters to mask the phenolate donor of salicylaldehyde-based chelators. The new prochelators liberate a tridentate thiosemicarbazone intracellularly upon reaction with abundant nucleophile glutathione (GSH). A 5bromo-substituted salicylaldehyde thiosemicarbazone (STC4) was selected for the chelator unit because of its antiproliferative activity at low micromolar levels in a panel of six cancer cell lines. The arylsulfonate prochelators were assessed in vitro with respect to their stability, ability to abolish metal binding, and reactivity in the presence of GSH. Cell-based assays indicated that the arylsulfonatemasked prochelators present higher antiproliferative activities relative to the parent compound after 24 h. The activation and release of the chelator intracellularly were corroborated by assays of cytosolic iron binding and iron supplementation effects as well as cell cycle analysis. This study introduces the 1,3,4-thiadiazole sulfonate moiety to mask the phenolate donor of an iron chelator and impart good solubility and stability to prochelator constructs. The reactivity of these systems can be tuned to release the chelator at high glutathione levels, as encountered in several cancer phenotypes.

show abstract

“…Cephalosporins of the initial generation include cefazolin and cefazedone. [4][5][6] The =NÀ CÀ SÀ group and the high aromaticity of the ring [7][8][9][10][11][12][13][14] have been linked to a variety of biological activities of 1,3,4-thiadiazole derivatives, including anticancer, antimicrobial, antiviral, antidepressant, anti-diabetic, analgesic, antihypertensive, anti-inflammatory, local anesthetic, and kinesis inhibitors. Also, offers this five-membered ring structure with excellent in vivo stability as well as minimal toxicity to higher vertebrates, including people.…”

Section: Introductionmentioning

confidence: 99%

Synthesis, Molecular Docking, and Antitumor Activity of 1,3,4‐Thiadiazole‐Based Heterocycles against Hepatocellular Carcinoma

et al. 2023

View full text Add to dashboard Cite

Numerous aminothiadiazole‐based compounds have been extensively employed as pharmaceuticals to treat a variety of ailments, leading to a flurry of new discoveries. It takes novel synthetic techniques to prepare new aminothiadiazole derivatives from enaminonitrile derivative 4, which was formerly an important step in the synthesis of pyrazole, isoxazole, and pyrimidine derivatives (6, 8, and 10). For the production of triazolo, imidazolo, and pyrazolo pyrimidine derivatives, enaminonitrile 4 also has shown chemical activity toward various N‐nucleophiles, such as heterocyclic amines (12, 14, and 16). As a result of cyclo‐condensing enaminonitrile precursor 4 with a variety of carbon and oxygen nucleophiles, certain complex, polyfunctional substituted fused 2‐pyridone and chromenone derivatives containing thiadiazole molecules were produced (18, 20, 22, and 25). Next, the cytotoxic effect of the entitled compounds against HepG2 and MCF7 has been reported, followed by an in‐vivo study on hepatocellular carcinoma (HCC) HepG2 with the compounds that showed the lowest IC50 values. In addition to molecular docking into the FGFR 4 active site (PDB: 4XCU), the bioavailability of the active compounds in accordance with Lipinski's rule of five has been shown.

show abstract

Synthetic and anti-cancer activity aspects of 1, 3, 4-thiadiazole containing bioactive molecules: A concise review

Cited by 15 publications

References 61 publications

4-Methyl-7-((2-((5-methyl-1,3,4-thiadiazol-2-yl)thio)ethyl)thio)-coumarin

4-Methyl-7-((2-((5-methyl-1,3,4-thiadiazol-2-yl)thio)ethyl)thio)-coumarin

Thiol-Reactive Arylsulfonate Masks for Phenolate Donors in Antiproliferative Iron Prochelators

Synthesis, Molecular Docking, and Antitumor Activity of 1,3,4‐Thiadiazole‐Based Heterocycles against Hepatocellular Carcinoma

Contact Info

Product

Resources

About