2-aminobenzothiazole Derivatives Research Articles

Novel 2-Aminobenzothiazole Derivatives: Docking, Synthesis, and Biological Evaluation as Anticancer Agents.

Sixteen novel 2-aminobenzothiazole compounds with different amines or substituted piperazine moieties were designed, synthesized, and tested using various methods. Potential interactions were assessed by docking new compounds in the adenosine triphosphate (ATP) binding domain of the PI3Kγ enzyme (PDB code: 7JWE) by nucleophilic substitution or solvent-free/neat fusion for docked compound synthesis. Final 2-aminobenzothiazole compounds were characterized by direct probe gas chromatography-mass spectrometry (GC-MS), proton (1H-NMR), carbon-13 (13C-NMR), and attenuated total reflectance-infrared Fourier transform infrared (ATR FT-IR). The synthesized compounds were investigated for anticancer activities on lung cancer (A549) and breast cancer (MCF-7) cell lines. The compounds' PI3Kγ inhibition was evaluated at a 100 μM concentration. 4-Nitroaniline and piperazine-4-nitroaniline combination in OMS5 and OMS14 reduced lung and breast cancer cell line growth. IC50 values for OMS5 and OMS14, the strongest compounds, ranged from 22.13 to 61.03 μM. OMS1 and OMS2 inhibited PI3Kγ at the highest rates (47 and 48%, respectively) at a 100 μM concentration. Results show that the PI3Kγ enzyme suppression is not the main mechanism behind these OMS5 and OMS14 anticancer effects. CDK2, Akt, mTOR, and p42/44 MAPK are affected. EGF receptor suppression matters. AKT1, AKT3, CDK1/cyclin B, PDK1 direct, PIK3CA E542 K/PIK3R1 (p110 α/p85 α), PIK3CD/PIK3R1 (p110 δ/p85 α), and PKN inhibition were measured to evaluate the possible mechanism of compound OMS14. PIK3CD/PIK3R1 (p110 δ/p85 α) is the most, with 65% inhibition, suggesting a possible mechanism of anticancer properties. Furthermore, the NCI 60-cell line inhibition demonstrates promising broad anticancer inhibition against numerous cancer cell lines of OMS5 and OMS14, which could be good lead compounds for future development.

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

Cancer remains a worldwide healthcare undertaking, demanding continual innovation in anticancer drug development due to frequent drug resistance and adverse effects associated with existing therapies. The benzothiazole compounds, particularly 2-aminobenzothiazole derivatives, have attracted interest for their versatility in generating novel anticancer agents. This study explores the synthesis, and anticancer evaluation of new pyrimidine-based 2-aminobenzothiazole derivatives. A range of synthetic methods have been developed based on the reaction of 2-benzothaizolyl guanidine with various reagents such as α,β-unsaturated carbonyl, 2-cyano-three-(dimethylamino)-N-acrylamide, β-diketones, β-keto esters, and S,S ketene dithioacetals. Human tumour cell lines such as HepG2, HCT116, and MCF7 were used in in vitro cytotoxicity studies, and the results showed that several of the synthesized compounds were more potent than the standard drug, 5-fluorouracil, in terms of cell viability% with low IC50. Furthermore, the computed drug likeness and ADMET properties of the most potent synthesized compounds suggest their potential as promising candidates for further development, with favorable bioavailability and pharmacokinetic profiles.

New 2-aminobenzothiazole derivatives: Design, synthesis, anti-inflammatory and ulcerogenicity evaluation

Two series of twenty diversely substituted benzothiazole amides were designed and synthesized aiming to obtain derivatives with potential anti-inflammatory activity and decreased GIT ulceroginicity. All the synthesized compounds were in-vivo screened for their anti-inflammatory activity using carrageenan induced rat hind paw edema model. Results revealed that compounds 3h and 6a were the most potent ones with remarkable GIT tolerability compared to indomethacin (ED50 = 0.012, 0.016 and 0.015 mmol/kg, respectively). Moreover, compounds 3h and 6a ulcerogenic investigation proved ulcer index= 0 at the first 2 doses (0.01, 0.02 mmol/kg) and surpassing the third dose (0.03 mmol/kg) for 6a only, respectively. In vitro COX-1/COX-2 isozyme selectivity testing revealed the best selectivity index for compound 6a (SI= 3.10) among the investigated compounds compared to celecoxib (SI= 11.89), which was further confirmed with the molecular docking study.

Cu(II)/citric acid grafted to chitosan by dendritic units of melamine as a novel and highly efficient heterogeneous catalyst for the synthesis of 2-aminobenzothiazole derivatives

In this paper, a new cross-linked chitosan by G1 dendrimer from melamine terminated by citric acid groups to support Cu(II) nanoparticles (CS@CA-Me-CA@Cu) was designed and prepared. Subsequently, the prepared nanocomposite was characterized using different spectroscopic, microscopic and analytical techniques such as FTIR, XRD, FESEM, TGA and EDX. The supramolecular CS@CA-Me-CA@Cu demonstrates higher thermal and chemical stability than its components. In addition, in order to investigate the catalytic performance of the CS@CA-Me-CA@Cu bio-based nanocomposite it was used, as a Lewis acidic and green heterogeneous catalyst, for the preparation of 2-aminobenzothiazole derivatives under green conditions. Also, other advantages of this new bio-based nanocomposite include easy preparation, high catalytic activity, recyclability, and reuse with a gradual decreasing in its catalytic activity.

Synthesis, Computational Study, and Anticonvulsant Activity of Newly Synthesized 2-aminobenzothiazole Derivatives

Background:Despite the fact that anticonvulsant drugs targeting multiple targets have been used in the health center, their effectiveness and tolerability in the treatment of seizures have not improved much. As a result, innovative anticonvulsant medicines are still needed urgently to overcome the significant toxicity of currently existing medications.Objective:This study aimed to synthesize 2-aminobenzothiazole derivatives as anticonvulsant agents, compute physicochemical parameters, and conduct a docking investigation.Methods:Condensing 4-(2-(benzo[d]thiazole-2-ylamino) acetamido) benzoyl chloride with substituted phenols in acetone in anhydrous potassium carbonate in the presence of potassium iodide in dry acetone yielded benzothiazole derivatives. IR and NMR spectroscopy were used to characterize the structures of freshly synthesized substances. To estimate their drug-like candidates, a number of molecular attributes of these derivatives were computed. The carbonic anhydrase enzyme was used to perform molecular docking on these synthesized compounds. The synthetic compounds were tested for biological activity, such as anticonvulsant activity and enzyme inhibitor activity for carbonic anhydrase.Results:The findings showed that V-5 (4-chlorophenyl 4-(2-(benzo[d]thiazol-2-ylamino)acetamido)benzoate) had the strongest anticonvulsant effect out of all the eight target compounds.Conclusion:The outcome of this research was that V-5 could be a promising new lead molecule for the development of anticonvulsant drugs.

A green aerobic Fe(lll) catalyzed base-free synthesis of 2-aminobenzothiazoles in water

An Fe(III) catalyzed, efficient methodology for the synthesis of 2-aminobenzothiazole derivatives in water was established. This mild, base-free, one-pot strategy showcases the reaction of readily available 2-bromophenyl isothiocyanate with a broad range of substituted amines such as aliphatic, aromatic, primary, secondary and cyclic amines under air. Notably, the reaction afforded the corresponding products with moderate to excellent yields in green conditions. The present optimization was found to be highly desirable for aliphatic amine substrates. Moreover, the catalyst could be successfully recovered and recycled for a minimum of 5 times without much loss in efficiency.

Synthesis and Characterization of Proton Transfer Salts of 2-Aminobenzothiazole Derivatives

Özet
 Bu çalışmada, önce (E)-4-okso-4-(3-sülfamoyilfenil)amino)büt-2-enoik asit (Habsmal), maleik anhidrit (mal) ile 3-aminobenzensulfonamit’in (abs) tepkimesinden elde edilmiştir. Daha sonra Habsmal ile 2-aminobenzotiyazol (abt) (1) ve 2-amino-6-etoksibenzotiyazol’ün (EtOabt) (2) tuzları sentezlenmiştir. Ayrıca 5-sülfosalisilik asit (H3ssa) ile 2-amino-6-hidroksobenzotiyazol (HOabt) (3) ve 2-amino-6-nitrobenzotiyazol’ün (NO2abt) (4) tepkimelerinden proton transfer tuzları elde edilmiştir. Amorf halde elde proton transfer tuzlarının yapıları, elementel analiz, NMR (1H ve 13C), FT-IR, yük denkliği ve daha önceki çalışmalar ile önerilmiştir. Bu analiz sonuçlarına göre asit ve baz birleşme oranları 1:1 olarak bulunmuştur.

Design, synthesis, biological evaluation, and in silico studies of 2-aminobenzothiazole derivatives as potent PI3Kα inhibitors.

A new series of 2-aminobenzothiazole derivatives was designed, synthesized and evaluated for their anticancer activity against the MCF7, MDAMB-231, and HepG2 cancer cell lines. All synthesized derivatives (8a-8n) demonstrated moderate to high anticancer activity against the tested cell lines. As the most potent compound in the series, compound 8i displayed excellent inhibitory potency with an IC50 value of 6.34 μM and compound 8m displayed an IC50 value of 8.30 µM against the MCF7 cell line compared to the standard drug HS-173 (IC50 = 10.25 μM). PI3K enzyme activity assays demonstrated that compound 8i is highly selective against PI3Kα, with an IC50 value of 1.03 nM. Wound healing assays and cell cycle analysis of compounds 8i and 8m revealed that both compounds suppressed the migration of MCF7 cells and induce cell cycle arrest in the S phase. In the cell death assay, compound 8i was revealed to induce apoptosis in a dose-dependent pattern; further Western blot assays revealed that compound 8i obviously decreases the levels of the antiapoptotic proteins Bcl-xL and Mcl-1. Downregulation of the expression of p-Akt confirmed the PI3K inhibitory activity of compound 8i. The molecular docking and molecular dynamicssimulation studies performed were found in agreement with the PI3Kα inhibitory activity assessments performed experimentally.

Eelectrosynthesis of benzothiazole derivatives via C–H thiolation

Abstract Benzothiazole derivatives are essential intermediates in synthesizing a wide variety of medical and pharmaceutical compounds, and there is a great demand for a simple and efficient method to synthesize benzothiazoles under mild reaction conditions. Organic electrosynthesis as an energy-efficient process represents an environmentally benign and safer method than traditional methods for organic synthesis. Herein, we present bromine-free and straightforward synthesis of 2-amino benzothiazole derivatives via the reaction of aniline derivatives and ammonium thiocyanate using electrosynthesis in the presence of sodium bromide both as an electrolyte and as a brominating agent at room temperature in isopropyl alcohol (i-PrOH) as a solvent. The reaction of ammonium thiocyanate via C–H thiolation routes, using various aniline derivatives, resulted in a simple, green, and bromine-free synthesis of 2-amino benzothiazole in moderate to good yields under mild reaction conditions. Riluzole drug can be produced using the same procedure in moderate yields.

High-Performance UV-Vis Light Induces Radical Photopolymerization Using Novel 2-Aminobenzothiazole-Based Photosensitizers.

The popularity of using the photopolymerization reactions in various areas of science and technique is constantly gaining importance. Light-induced photopolymerization is the basic process for the production of various polymeric materials. The key role in the polymerization reaction is the photoinitiator. The huge demand for radical and cationic initiators results from the dynamic development of the medical sector, and the optoelectronic, paints, coatings, varnishes and adhesives industries. For this reason, we dealt with the subject of designing new, highly-efficient radical photoinitiators. This paper describes novel photoinitiating systems operating in UV-Vis light for radical polymerization of acrylates. The proposed photoinitiators are composed of squaraine (SQ) as a light absorber and various diphenyliodonium (Iod) salts as co-initiators. The kinetic parameters of radical polymerization of trimethylolpropane triacrylate (TMPTA), such as the degree of double bonds conversion (C%), the rate of photopolymerization (Rp), as well as the photoinitiation index (Ip) were calculated. It was found that 2-aminobenzothiazole derivatives in the presence of iodonium salts effectively initiated the polymerization of TMPTA. The rates of polymerization were at about 2 × 10−2 s−1 and the degree of conversion of acrylate groups from 10% to 36% were observed. The values of the photoinitiating indexes for the most optimal initiator concentration, i.e., 5 × 10−3 M were in the range from 1 × 10−3 s−2 even to above 9 × 10−3 s−2. The photoinitiating efficiency of new radical initiators depends on the concentration and chemical structure of used photoinitiator. The role of squaraine-based photoinitiating systems as effective dyeing photoinitiators for radical polymerization is highlighted in this article.

N-Iodosuccinimide mediated intramolecular oxidative C(sp 2)-S bond formation for the synthesis of 2-aminobenzothiazole derivatives

An extremely efficient synthetic method for the preparation of 2-aminobenzothiazole derivatives starting from arylthioureas by using N-iodosuccinimide has been reported. This protocol features a mild reaction conditions, a short reaction time, and metal-free oxidative conditions for C (sp 2)-S bond construction.

Phenanthroline-functionalized porous aromatic framework: An efficient heterogeneous catalyst for the tandem reaction of 2-iodoanilines and isothiocyanates in water

Abstract A phenanthroline-functionalized porous aromatic framework (Phen-PAF) was synthesized by the Sonogashira reaction between 1,3,5-tris-(4-ethynylphenyl)benzene (TEB) and 3,8-dibromo-1,10-phenanthroline (DPHEN). Phen-PAF was demonstrated to have highly catalytic effect on the tandem reaction between 2-iodoanilines and isothiocyanates, leading to a series of 2-aminobenzothiazole derivatives in good to excellent yield (80–99%). The reaction was environmentally friendly for utilizing water as solvent under mild heating conditions. More importantly, Phen-PAF catalyst can be recycled by simple filtration and drying. Phen-PAF kept its robust chemical structure and catalytic activity for at least 5 catalytic cycles, which was in accordance with sustainable chemistry. Phen-PAF was, what has been reported so far, the first organic porous heterogeneous catalyst towards the tandem reaction of 2-iodoanilines and isothiocyanates with environmentally friendly solvent, which may enlighten us to design more function-oriented PAF materials as heterogeneous catalysts towards various organic reactions.

Preparation of benzo[4,5]thiazolo[3,2-a]chromeno[4,3-d]pyrimidin-6-one derivatives using MgO-MgAl2O4 composite nano-powder

MgO-MgAl2O4 nanocomposite was prepared from the co-precipitation of Mg(NO3)2 and Al(NO3)3 salts, characterized by X-ray diffraction (XRD), transmission electron microscopy (TEM), energy-dispersive X-ray spectroscopy (EDS) and fourier transform infrared spectroscopy (FTIR) techniques and evaluated in the synthesis of thirty five derivatives of benzo[4,5]thiazolo[3,2-a]chromeno[4,3-d]pyrimidin-6-ones (d1-d34) via the multi-component reaction of 4-hydroxycoumarins, aldehydes, and 2-aminobenzothiazole derivatives under solvent free condition. The catalytic activity of MgO-MgAl2O4 nanocomposite and the synthesis of the above mentioned compounds were investigated under thermal solvent free (times: 1.4–3 h; yields: 75–95%), ultrasonic irradiation (US) conditions (times: 1–2.5 h; yields: 69–97%) and using high-speed ball milling (HSBM) technique (times: 0.7–2.5 h; yields: 67–97%). In all cases, the products were obtained in excellent yields. Nuclear Magnetic Resonance (NMR) and MASS spectroscopy were used to characterize the structure of the desired product. The mechanism for the preparation of compounds d1-d34 was proposed and confirmed by 1H NMR investigations.

Design Synthesis and Biological Evaluation of Dithiocarbamate Substituted 2-Aminobenzothiazole Derivatives as Proviral Integration Site of Moloney Murine Leukaemia Virus 1 Kinase Inhibitors

In the present study, we intended to synthesize novel derivatives against Proviral Integration site of Moloney murine leukaemia virus 1 kinase, a biomarker over expressed in numerous malignancies. A novel series of derivatives containing dithiocarbamate moiety as a side chain at the second position of 2-amino benzothiazole nucleus were synthesized and characterized by spectral analysis. From the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide Assay performed, compounds 4a, 4c and 4h of the series emerged as potent anticancer agents against SK-OV-3 cell lines with half-maximal inhibitory concentration value of 34.52±0.5 μM, 34.28±0.06 μM and 29.17±0.66 μM, respectively (p<0.05) compared to standard drug doxorubicin’s half-maximal inhibitory concentration value 17.07±0.05 μM. From the anti-mitotic activity studies all the compounds showed good to moderate activity with half-maximal inhibitory concentration values ranging from 1.88±0.66 to 20.91±0.34 μM, (p<0.05). The evaluation of in silico absorption, distribution, metabolism, excretion, and toxicity and molecular descriptors, proved that the synthesized compounds posses drug like properties and are safer to the normal cells. From the molecular docking studies, compounds 4a, 4c, 4h showed good binding affinity with PIM 1 Kinase protein and retained required amino acid interaction similar to the co-crystal. Hence, this study proves 2 amino benzothiazole dithiocarbamate derivatives can be used as encouraging leads as PIM 1 Kinase inhibitors).

Synthesis of novel 2-aminobenzothiazole derivatives as potential antimicrobial agents with dual DNA gyrase/topoisomerase IV inhibition.

Novel benzothiazole-based compounds were designed and synthesized as potential antimicrobial agents with dual DNA gyrase/topoisomerase IV inhibitory activity. The structures of the newly synthesized compounds were established on the basis of spectral (IR, NMR, MS) and elemental analyses. Most of the studied compounds possessed significant antimicrobial activity against tested bacteria and fungi. Compounds 4b and 7a were much more potent than reference standard ciprofloxacin against methicillin-resistant Staphylococcus aureus (MRSA) and a multi-drug resistant clinical isolate of Enterococcus faecium. Moreover, 7a was equipotent to nystatin against clinical isolate of Candida albicans. Both 4b and 7a inhibited DNA gyrase and topoisomerase IV at low micromolar levels and also displayed safety profiles much better than that of novobiocin in cytotoxicity assay.

New Hybrids with 2-aminobenzothiazole and Azelayl Scaffolds: Synthesis, Molecular Docking and Biological Evaluation

Novel compounds containing both benzothiazole and azelayl scaffolds were synthesized through Schotten Baumann type reaction between azelayl chloride methyl ester and a series of 2-aminobenzothiazole derivatives bearing different substituents on the aromatic carbocyclic ring. The design of the new hybrids was inspired by their analogy with the structure of some HDAC inhibitors, such as Vorinostat and 9-hydroxystearic acid. Molecular docking on some compounds predicted an activity as inhibitors of HDAC, and this prediction was confirmed by in vitro essays on a human colon cancer cells line (HT 29). The antimicrobial activity against some representative human pathogens and several Lactobacillus and Bifidobacterium strains isolated from human microbiotas was also evaluated. The new hybrids showed antiproliferative activity on cancer cells while no antimicrobial activity was observed in the range of concentrations used for cancer cells and this finding might represent an important tool in the fight against cancer minimizing some side effects on the microbiotas typical of an anticancer treatment. Keywords: 2-Aminobenzothiazole, azelaic acid, schotten baumann, colon cancer, histone deacetylase inhibitors, 9-hydroxystearic acid, vorinostat.

Synthesis, characterization, and pharmacological evaluation of the proton transfer salts of 2-aminobenzothiazole derivatives with 5-sulfosalicylic acid and their Cu(II) complexes

Two proton transfer compounds, formed between 2-aminobenzothiazole derivatives (2-aminobenzothiazole (abt) and 2-amino-6-ethoxybenzothiazole (EtOabt)) and 5-sulfosalicylic acid dihydrate (H3ssa) as parent compounds, (Habt)+(H2ssa)− (1) and (HEtOabt)+(H2ssa)− (2) and their Cu(II) complexes (3 and 4, respectively) have been prepared and characterized using spectroscopic techniques. The single crystal X-ray diffraction method has been also applied to 3 and 4. Although 3 has a distorted octahedral form, 4 exhibits a distorted square pyramidal geometry. All compounds, including saline and diclofenac sodium as standards, have been evaluated pharmacologically for their anti-inflammatory and analgesic activities in rats and mice. Parent compounds (abt, EtOabt, and H3ssa) 3 and 4 show significant anti-inflammatory and analgesic activities as compared with control compounds.

Palladium-catalyzed Tandem Synthesis of 2-Aminobenzothiazoles Starting from Unreactive 2-Chloroanilines

A simple and efficient protocol for the synthesis of 2-aminobenzothiazole derivatives is described. 2-Chloroanilines were treated with thiocarbamoyl chloride in the presence of Pd(dba)2 and t-BuOK to afford the corresponding 2-aminobenzothiazoles in good to excellent yield via a tandem manner.

Optimization and biological evaluation of 2-aminobenzothiazole derivatives as Aurora B kinase inhibitors

A strong relationship between abnormal functions of Aurora kinases and tumorigenesis has been reported for decades. Consequently, Aurora kinases serve as potential targets for anticancer agents. Here, we identified aminobenzothiazole derivatives as novel inhibitors of Aurora B kinase through bioisosteric replacement of the previous inhibitors, aminobenzoxazole derivatives. Most of the urea-linked aminobenzothiazole derivatives showed potent and selective inhibitory activity against Aurora B kinase over Aurora A kinase. Molecular modeling indicated that compound 15g bound well to the active site of Aurora B kinase and formed the essential hydrogen bonds. The potent compounds, 15g and 15k, were selected, and their biological effects were evaluated using HeLa cell lines. It was found that these compounds inhibited the phosphorylation of histone H3 at Ser10 and induced G2/M cell cycle arrest. We suggest that the reported compounds have the potential to be further developed as anticancer therapeutics.

Antimicrobial, antioxidant and SOD activities of copper(II) complexes derived from 2-aminobenzothiazole derivatives

A series of Cu(II) complexes have been synthesized from bidentate Schiff base ligands (by condensation of Knoevenagel condensate of acetoacetanilide (obtained from substituted benzaldehydes and acetoacetanilide) and 2-aminobenzothiazole). They were characterized by elemental analysis, IR, 1H NMR, 13C NMR, UV–vis., molar conductance, magnetic moment, ESR spectra and electrochemical studies. Based on the magnetic moment, ESR, and electronic spectral data, a distorted square planar geometry has been suggested for the complexes. Antibacterial and antifungal screening of the ligands and their complexes reveal that all the complexes show higher activities than the ligands. The antioxidant activities of the ligands and complexes were determined by superoxide and hydroxyl radical scavenging methods in vitro, indicating that the complexes exhibit more effective antioxidant activity than the ligands alone. The results show that the Cu(II) complexes also have similar superoxide dismutase activity to that of native Cu, Zn-SOD. All complexes exhibit suitable Cu(II)/Cu(I) redox potential (E1/2) to act as synthetic antioxidant enzyme mimics.