Recent advances and SAR study of 2-substituted benzothiazole scaffold based potent chemotherapeutic agents

Haider, Kashif; Shrivastava, Neelima; Pathak, Ankita; Dewangan, Rikeshwer Prasad; Yahya, Shaikh; Yar, Mohammad Shahar

doi:10.1016/j.rechem.2021.100258

Cited by 22 publications

(13 citation statements)

References 100 publications

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“…Furthermore, during the last years, there have been several attempts to develop different benzothiazole surrogates with unique and promising profile as antitumor agents through inhibition of protein kinases 43–46 . In this context, 2-aminobenzothiazole derivatives were found to be very effective scaffolds as will be shown in this work 47 .…”

Section: Introductionmentioning

confidence: 99%

New benzothiazole hybrids as potential VEGFR-2 inhibitors: design, synthesis, anticancer evaluation, and in silico study

Al‐Sanea

Hamdi

Mohamed

et al. 2023

Journal of Enzyme Inhibition and Medicinal Chemistry

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A new series of 2-aminobenzothiazole hybrids linked to thiazolidine-2,4-dione 4a–e , 1,3,4-thiadiazole aryl urea 6a–d, and cyanothiouracil moieties 8a–d was synthesised. The in vitro antitumor effect of the new hybrids was assessed against three cancer cell lines, namely, HCT-116, HEPG-2, and MCF-7 using Sorafenib (SOR) as a standard drug. Among the tested compounds, 4a was the most potent showing IC50 of 5.61, 7.92, and 3.84 µM, respectively. Furthermore, compounds 4e and 8a proved to have strong impact on breast cancer cell line with IC50 of 6.11 and 10.86 µM, respectively. The three compounds showed a good safety profile towards normal WI-38 cells. Flow cytometric analysis of the three compounds in MCF-7 cells revealed that compounds 4a and 4c inhibited cell population in the S phase, whereas 8a inhibited the population in the G1/S phase. The most promising compounds were subjected to a VEGFR-2 inhibitory assay where 4a emerged as the best active inhibitor of VEGFR-2 with IC50 91 nM, compared to 53 nM for SOR. In silico analysis showed that the three new hybrids succeeded to link to the active site like the co-crystallized inhibitor SOR.

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Section: Introductionmentioning

confidence: 99%

New benzothiazole hybrids as potential VEGFR-2 inhibitors: design, synthesis, anticancer evaluation, and in silico study

Al‐Sanea

Hamdi

Mohamed

et al. 2023

Journal of Enzyme Inhibition and Medicinal Chemistry

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“…Benzothiazole is another emerging privileged structure in anticancer research [ 16 , 17 , 18 ]. The synthesis and anticancer activity of 2-benzothiazole hydrazones towards human cancer cell lines has been reported [ 19 ], with most compounds showing a good cytotoxic profile and a few revealing IC 50 values in the nM range in HL-60 (leukemia cancer cells).…”

Section: Introductionmentioning

confidence: 99%

Liposomal Formulations of a New Zinc(II) Complex Exhibiting High Therapeutic Potential in a Murine Colon Cancer Model

Ribeiro

Albino

Ferreira

et al. 2022

IJMS

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Colorectal cancer is the second leading cause of cancer-related mortality. Many current therapies rely on chemotherapeutic agents with poor specificity for tumor cells. The clinical success of cisplatin has prompted the research and design of a huge number of metal-based complexes as potential chemotherapeutic agents. In this study, two zinc(II) complexes, [ZnL2] and [ZnL(AcO)], where AcO is acetate and L is an organic compound combining 8-hydroxyquinoline and a benzothiazole moiety, were developed and characterized. Analytical and spectroscopic studies, namely, NMR, FTIR, and UV-Vis allowed us to establish the complexes’ structures, demonstrating the ligand-binding versatility: tetradentate in [ZnL(AcO)] and bidentate in [ZnL2]. Complexes were screened in vitro using murine and human colon cancer cells cultured in 2D and 3D settings. In 2D cells, the IC50 values were <22 µM, while in 3D settings, much higher concentrations were required. [ZnL(AcO)] displayed more suitable antiproliferative properties than [ZnL2] and was chosen for further studies. Moreover, based on the weak selectivity of the zinc-based complex towards cancer cell lines in comparison to the non-tumorigenic cell line, its incorporation in long-blood-circulating liposomes was performed, aiming to improve its targetability. The resultant optimized liposomal nanoformulation presented an I.E. of 76% with a mean size under 130 nm and a neutral surface charge and released the metal complex in a pH-dependent manner. The antiproliferative properties of [ZnL(AcO)] were maintained after liposomal incorporation. Preliminary safety assays were carried out through hemolytic activity that never surpassed 2% for the free and liposomal forms of [ZnL(AcO)]. Finally, in a syngeneic murine colon cancer mouse model, while free [ZnL(AcO)] was not able to impair tumor progression, the respective liposomal nanoformulation was able to reduce the relative tumor volume in the same manner as the positive control 5-fluorouracil but, most importantly, using a dosage that was 3-fold lower. Overall, our results show that liposomes were able to solve the solubility issues of the new metal-based complex and target it to tumor sites.

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“…Benzothiazoles and its derivatives attracted the interest of medicinal chemists because of their extensive variety of pharmacological properties, including anti-inflammatory [ 1 , 2 , 3 ], antimicrobial [ 4 , 5 , 6 , 7 ], anticancer [ 8 , 9 , 10 ], antitubercular [ 11 , 12 ], antidiabetic [ 13 ], antioxidant [ 14 , 15 ], antiviral [ 16 , 17 , 18 ], antileishmanial [ 19 ], and others [ 20 , 21 ].…”

Section: Introductionmentioning

confidence: 99%

Experimental and In Silico Evaluation of New Heteroaryl Benzothiazole Derivatives as Antimicrobial Agents

Зубенко

Карцев²,

Petrou

et al. 2022

Antibiotics

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In this manuscript, we describe the design, preparation, and studies of antimicrobial activity of a series of novel heteroarylated benzothiazoles. A molecular hybridization approach was used for the designing compounds. The in vitro evaluation exposed that these compounds showed moderate antibacterial activity. Compound 2j was found to be the most potent (MIC/MBC at 0.23–0.94 mg/mL and 0.47–1.88 mg/mL) On the other hand, compounds showed good antifungal activity (MIC/MFC at 0.06–0.47 and 0.11–0.94 mg/mL respectively) with 2d being the most active one. The docking studies revealed that inhibition of E. coli MurB and 14-lanosterol demethylase probably represent the mechanism of antibacterial and antifungal activities.

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Recent advances and SAR study of 2-substituted benzothiazole scaffold based potent chemotherapeutic agents

Cited by 22 publications

References 100 publications

New benzothiazole hybrids as potential VEGFR-2 inhibitors: design, synthesis, anticancer evaluation, and in silico study

New benzothiazole hybrids as potential VEGFR-2 inhibitors: design, synthesis, anticancer evaluation, and in silico study

Liposomal Formulations of a New Zinc(II) Complex Exhibiting High Therapeutic Potential in a Murine Colon Cancer Model

Experimental and In Silico Evaluation of New Heteroaryl Benzothiazole Derivatives as Antimicrobial Agents

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