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Three-dimensional representation showed interactions of compound 20b and the DHFR enzyme pocket amino acids.
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Background
Nowadays, cancer is an important public health problem in all countries. Limitations of current chemotherapy for neoplastic diseases such as severe adverse reactions and tumor resistance to the chemotherapeutic drugs have been led to a temptation for focusing on the discovery and development of new compounds with potential anticancer act...
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This study focussed on composite boards made from Elaeis guineesis empty fruit bunches (EFB). The EFB supplied by a smallholder oil palm planter in Kuala Krai, Kelantan. The fibre cutter and crusher were used in turning the EFB into smaller size particles. They were screened with four-tier sieve shaker used to remove the oversize particles and impu...
Abundance of oil palm trunks (OPT) can be obtained from the replanting activities that can be converted into value-added products. One of the sectors that can beneficial from this is bio-composite. Low-density sandwich board (SB) consisting of a core-board (CB) overlaid with an oil palm veneer face was produced and studied in this paper. Effect of...
Citations
... These compounds demonstrate the diverse ways in which thiazole-containing drugs can exhibit anticancer activities [24][25][26][27][28][29][30][31][32]. Recently, the strategy of molecular hybridization, combining multiple bioactive fragments into one molecule, has become an effective and promising approach in novel drug development for cancer treatment [33][34][35][36]. ...
... Motivated by the significant biological properties of imidazole and thiazole derivatives and continuing our work in synthesizing new bioactive heterocycles [27,[33][34][35][46][47][48][49][50][51][52][53][54], we developed an efficient method to create novel hybrid molecules containing both imidazole and thiazole rings. This method, utilizing DABCO as a catalyst, is distinguished by its short reaction time and high yields, making it an environmentally friendly and cost-effective approach in the field of medicinal chemistry (Fig. 1). ...
Background
Given the inadequacies of current chemotherapy, there is a need for more effective anticancer agents. Imidazole and thiazole compounds have demonstrated significant biological activity, making them promising candidates
Aims and Objective
This study investigates the anticancer potential of imidazole and thiazole derivatives, focusing on liver cancer. The aim is to synthesize bis-imidazole-thiazole hybrids and evaluate their efficacy as anticancer agents against hepatocellular carcinoma.
Methods
The hybrids were synthesized using (2,2'-((1,4-phenylenebis(2-mercapto-4-methyl-1H-imidazole-1,5-diyl))bis(ethan-1-yl-1-ylidene))bis(hydrazine-1-carbothioamide), hydrazonoyl halides, and α-halo ketones, catalyzed by DABCO. This method is designed to be fast, yield high amounts of product, and be environmentally friendly. Structural confirmation was provided by FT IR, NMR, and MS spectroscopy.
Results
The synthesized hybrids were tested in vitro against HepG-2 and WI-38 cell lines. Compounds 16b, 14a, 16a, and 7b showed significant inhibitory activity, with IC50 values indicating strong inhibition comparable to or better than the standard drug Sorafenib.
Conclusion
The bis-imidazole-thiazole hybrids exhibit potent anticancer properties, particularly against hepatocellular carcinoma, making them potential candidates for future cancer therapies. Their selectivity and safety were further demonstrated by their effects on normal WI-38 human fibroblasts.
... 1,3,4-Thiadiazole and its derivatives are among the most extensively researched heterocyclic nuclei containing nitrogen and sulphur. They are known to be anticancer, antibacterial, anti-inflammatory, antihypertensive and anti-viral, analgesic, antioxidant, diuretic and anticonvulsant agents [18][19][20][21][22][23][24][25]. Additionally, numerous studies have highlighted the exceptional anticancer properties of 1,3,4-thiadiazole derivatives, including Filanesib and compounds I-III (Fig. 2) [26][27][28][29][30]. Furthermore, drugs like Cefazedone and Cefazolin sodium, which also contain the 1,3,4-thiadiazole moiety, are recognized for their broadspectrum antibiotic effectiveness [31] (Fig. 2). ...
... [57][58][59][60] The aim of this work is to leverage the well-established biological activities of pyrazoles, thiazoles, and their bisderivatives, along with our expertise in synthesizing bioactive heterocyclic compounds. [61][62][63][64][65][66][67][68][69][70] We focused on the synthesis of a novel series of bis-thiazolyl-pyrazole derivatives (7a-h) by varying the functional groups X, Y, and Z (Figure 1) to optimize their inhibitory potential against α-glucosidase. Using readily available curcumin analogues (3) as starting materials, our goal is to develop more effective and safer α-glucosidase inhibitors, contributing to the advancement of improved treatments for diabetes and its complications. ...
Glucosidase inhibitors are critical for diabetes management, with pyrazoles and thiazoles emerging as effective options. This research highlights curcumin‐based pyrazole‐thiazole hybrids as potential inhibitors, synthesizing derivatives and evaluating their inhibitory capabilities. The study involved the synthesis of novel compounds using hydrazonoyl halides, confirmed through elemental and spectral analyses. The synthesized derivatives exhibited significant α‐glucosidase inhibition, with IC50 values ranging from 3.37±0.25 to 16.35±0.37 μM. Among them, compound 7e demonstrated the strongest inhibition at 3.37±0.25 μM, outperforming the standard drug acarbose (IC50=5.36±0.31 μM). In silico assessments and molecular docking using AutoDock Vina revealed strong interactions, particularly with compounds 7b, 7e, 7f, and 7g, indicating their potential as stable and effective inhibitors. The results suggest that the synthesized pyrazole‐thiazole hybrids hold promise as novel therapeutic agents for diabetes, warranting further exploration of their substituent effects for optimized inhibitor design.
... Due to the aforementioned reasons, and as a part of our ongoing research to develop new bioactive heterocycles [6][7][8][39][40][41][42][43][44][45][46][47][48][49][50][51], we report herein a simple and efficient synthesis of new thirteen indeno-pyridazine-thiazole hybrid using the 2-(4-cyano-3-oxo-2,3-dihydro-9H-indeno[2,1-c]pyridazin-9ylidene)-hydrazine-1-carbothioamide derivative and various laboratory available reagents (Fig. 3). ...
Background: Previous studies have reported various biological activities of indeno-pyridazine and thiazole derivatives, including antiviral activity and CoV-19 inhibition. In this paper, the authors aimed to design, synthesize, and characterize a novel series of indenopyridazinethiazoles, starting with 2-(4-cyano-3-oxo-2,3-dihydro-9H-indeno[2,1-c]pyridazin-9-ylidene)-hydrazine-1-car-bothioamide and available laboratory reagents. Methods: The strategy involved the synthesis of indeno[2,1-c]pyridazincarbothioamide, followed by its reaction with various hydrazonoyl chlorides and α-halocompounds (phenacyl bromides and α-chloroketones) to obtain the desired indenopyridazinethiazole derivatives. The synthesized structures were confirmed using IR, NMR, mass spectra, elemental analysis, and alternative synthesis when possible. Docking scores and poses of thirteen synthesized compounds were examined using Auto-Dock4.2.6 software against multiple targets of SARS-CoV-2, including 3C-like protease (3CL pro), helicase, receptor binding domain (RBD), papain-like protease (PL pro), neuropilin-1 (NRP-1), RNA-dependent RNA polymerase (RdRp), and human angiotensin-converting enzyme 2 (ACE2). Results: Docking predictions revealed that compound 13d exhibited high potency against 3CL pro and helicase, with docking scores of-10.9 and-10.5 kcal/mol, respectively. Compound 10c showed superior docking scores against RBD and ACE2, with values of-8.7 and-11.8 kcal/mol, respectively. Compounds 10a, 13c, and 7b demonstrated excellent docking scores against RdRp, PL pro , and NRP-1, with values of-10.3,-10.4, and-8.6 kcal/mol, respectively. Conclusion: The authors recommend further experimental assessments of compounds 13d, 10c, 10a, 13c, and 7b against SARS-CoV-2 multi-targets, considering their promising docking scores.
... Cytotoxicity assay. Mouse macrophage cell lines (RAW 264.7) were used in an inhibition experiment to assess the cytotoxicity of all seventeen substances [27]. To do this experiment, a sterile 96-well microtiter plate with 5×10 3 cells was filled with varying amounts of the drugs under examination. ...
Abstract—A series of novel 3,4,7- or 3,4,8-trisubstituted-3a,4-dihydro[1,2,3]triazolo[1,5-a] quinazolin-5(3H)-one
analogues was synthesized and characterized by using HRMS, 1H NMR and 13C NMR spectral data. All the compounds
were tested for their in vitro antitubercular activity by using the Microplate Alamar Blue Assay technique,
the minimum inhibitory concentration values of the most effective inhibitors were determined for Mycobacterium
tuberculosis H37Rv and H37Ra strains by using rifampicin, isoniazid and ethambutol as reference standards. Among
all synthesized compounds 7-chloro-3-(3-chloropyridin-4-yl)-4-methyl[1,2,3]triazolo[1,5-a]quinazolin-5(4H)-
one, 7-bromo-8-chloro-4-(4-fluorophenyl)-3-(3-methylpyridin-4-yl)[1,2,3]triazolo[1,5-a]quinazolin-5(4H)-one
and 7-bromo-4-(4-methoxyphenyl)-3-(3-methylpyridin-4-yl)-[1,2,3]triazolo[1,5-a]quinazolin-5(4H)-one exhibit
excellent in vitro antitubercular activity when compared to the reference standards. Further 7-bromo-8-chloro-
4-(4-fluorophenyl)-3-(3-methylpyridin-4-yl)[1,2,3]triazolo[1,5-a]quinazolin-5(4H)-one was evaluated for in vivo
antitubercular activity after post treatment in female BALB/c mice by determination of log10 colony formation
unit in lungs and spleen. Therefore, this compound could serve as the lead molecule for further development as
antitubercular agent.
Keywords: antitubercular activity, triazoloquinazolinone, H37Rv, H37Ra, female BALB/c mice
... This study aims to address the need for new therapeutic agents with improved efficacy and reduced toxicity. Based on our previous research on anticancer heterocyclic compounds, [59][60][61][62][63][64][65][66][67][68][69] we synthesized a new type of aromatase inhibitors by combining the pyridopyrimidine and 1,2,4-triazole structures, known for their ability to inhibit aromatase and possess anticancer properties. The synthesized compounds will be characterized using various spectroscopic techniques and evaluated in vitro using MTT assays against MCF-7 breast cancer cell lines (Figure 1). ...
Breast cancer remains a major global health issue, particularly affecting women and contributing significantly to mortality rates. Current treatments for estrogen receptor‐positive breast cancers, such as aromatase inhibitors, are effective but often come with side effects and resistance issues. This study addresses these gaps by targeting aromatase, an enzyme crucial for estrogen synthesis, which plays a pivotal role in breast cancer progression. The innovative approach involves synthesizing novel bis‐triazolopyridopyrimidines, designed to leverage the combined pharmacological benefits of pyridopyrimidine and 1,2,4‐triazole structures, known for their potent aromatase inhibition and anti‐cancer properties. These compounds were synthesized and characterized using ¹H‐NMR, ¹³C‐NMR, and MS spectral analyses, and their anticancer efficacy was evaluated through MTT assays against MCF‐7 breast cancer cell lines in vitro. Molecular docking analyses revealed strong binding energies with aromatase, particularly for compounds 5 b, 5 c, 10 a, and 10 b, indicating their potential as effective aromatase inhibitors. The study highlights these compounds as promising candidates for further development as therapeutic agents against breast cancer.
... The Chemistry at Harvard Molecular Mechanics (CHARMm) force field was used to minimize total energy and optimize ligands. The designed ligand structures were converted into the pdb file format by BIOVIA Discovery Studio Visualizer [17][18][19]. The preparation of protein was done by Discovery Studio 2019 Client. ...
Objective: To design novel series of 1,3,4 thiadiazoles and to evaluate their anti-mycobacterial potency via In silico modeling. Methods: In silico modeling comprising of Lipinski rule evaluation, ADMET prediction, Molecular docking and Simulation studies aimed to identify potent 1,3,4 thiadiazoles. Results: The various physiochemical parameters and molecular descriptors of the proposed 1,3,4 thiadiazoles were predicted. And they exhibited good binding score compared with standard drug INH. The simulation studies showed minimal fluctuation of the ligand receptor complexes. Conclusion: The MD simulation and binding affinity of designed 1,3,4 thiadiazoles proved their efficiency as InhA inhibitors. The potency of the selected derivatives can be confirmed by further in vitro and in vivo experiments.
... Additionally, also it was observed that the replacement of the methoxy group with chlorine led to a decrease in activity. [86] The 3-thiophene-2-yl-quinoline derivatives were substituted with isoxazole, triazole and phenyl rings to obtain potent scaffolds against EGFR-TK by Othmana et al., in 2019. One of the title 3-thiophene-2-yl-quinoline derivatives were prepared by reacting alcoholic group of (2-chloroquinolin-3-yl)(thiophen-2-yl)methanol with various benzyl derivatives and were evaluated for their anticancer activity against four human cancer cells lines such as HepG2, HeLa, MCF-7 and HCT-116. ...
Sulfur‐containing heterocyclic derivatives have been disclosed for binding with a wide range of cancer‐specific protein targets. Various interesting derivatives of sulfur‐containing heterocyclics such as benzothiazole, thiazole, thiophene, thiazolidinedione, benzothiophene, and phenothiazine, etc have been shown to inhibit diverse signaling pathways implicated in cancer. Significant progress has also been made in molecular targeted therapy against specific enzymes such as kinase receptors due to potential binding interactions inside the ATP pocket. Sulfur‐containing heterocyclic ring metal complexes i. e., benzothiazole, thiazole, thiophene, benzothiophene and phenothiazines are among the most promising active anticancer compounds. However, sulfur heteroaromatic rings, particularly thiophene, are of high structural alert due to their metabolism to reactive metabolites. The mere presence of a structural alert itself does not determine compound toxicity therefore, this review focuses on some specific findings that shed light on factors influencing the toxicity. In the current review, synthetic strategies of introducing the sulfur core ring in the synthesized derivatives are discussed with their structure‐activity relationships to enhance our understanding of toxicity mechanisms and develop safer therapeutic options. The sulfur‐containing marketed anticancer drugs included in this review direct the synthesis of novel compounds and will help in the development of potent, safer sulfur‐based anticancer drugs in near future.
... Several synthetic protocols for the preparation of 1,3,4-thiadiazole-containing bioactive compounds have been developed and summarised [2,8,17,[27][28][29][30][31][32][33], the main part based on ring-closure reactions. Variable procedures are applied, like intramolecular cyclization of thiosemicarbazides [15,25] or potassium salt of hydrazinodithio formate [34] in concentrated sulphuric acid, condensation of thiosemicarbazide with carboxylic acids [35], benzoic acids [36,37], or N-arylsulfonylated amino acids [38], thiocarbohydrazides with aldehydes [39], hydrazinecarbodithioates or thiosemicarbazones with hydrazonoyl chlorides [40], sulfonamide diazonium chlorides with phenacyl thiocyanate [41], etc. At the same time, methods using an already built 1,3,4-thiadiazole unit are also exploited. ...
A study on the functionalisation of 2-mercapto-5-methyl-1,3,4-thiadiazole has been conducted, yielding two series of products: 2-(ω-haloalkylthio)thiadiazoles and symmetrical bis-thiadiazoles, with variable chain lengths. The experimental conditions were optimised for each class of compounds by altering the base used and the reagents’ proportions, leading to the development of separate protocols tailored to their specific reactivity and purification needs. The target halogenide reagents and bis-thiadiazole ligands were obtained either as single products or as mixtures easily separable by chromatography. Characterisation of the products was performed using 1D and 2D NMR spectra in solution, complemented by single crystal X-ray diffraction (XRD) for selected samples, to elucidate their structural properties.
... Due to the aforementioned reasons, and as a part of our ongoing research to develop new bioactive heterocycles [6][7][8][39][40][41][42][43][44][45][46][47][48][49][50][51], we report herein a simple and efficient synthesis of new thirteen indeno-pyridazine-thiazole hybrid using the 2-(4-cyano-3-oxo-2,3-dihydro-9H-indeno[2,1-c]pyridazin-9ylidene)-hydrazine-1-carbothioamide derivative and various laboratory available reagents (Fig. 3). ...
Background
Previous studies have reported various biological activities of indeno-pyridazine and thiazole derivatives, including antiviral activity and CoV-19 inhibition. In this paper, the authors aimed to design, synthesize, and characterize a novel series of indenopyridazinethiazoles, starting with 2-(4-cyano-3-oxo-2,3-dihydro-9H-indeno[2,1-c]pyridazin-9-ylidene)-hydrazine-1-car-bothioamide and available laboratory reagents.
Methods
The strategy involved the synthesis of indeno[2,1-c]pyridazincarbothioamide, followed by its reaction with various hydrazonoyl chlorides and α-halocompounds (phenacyl bromides and α-chloroketones) to obtain the desired indenopyridazinethiazole derivatives. The synthesized structures were confirmed using IR, NMR, mass spectra, elemental analysis, and alternative synthesis when possible. Docking scores and poses of thirteen synthesized compounds were examined using Auto-Dock4.2.6 software against multiple targets of SARS-CoV-2, including 3C-like protease (3CLpro), helicase, receptor binding domain (RBD), papain-like protease (PLpro), neuropilin-1 (NRP-1), RNA-dependent RNA polymerase (RdRp), and human angiotensin‐converting enzyme 2 (ACE2).
Results
Docking predictions revealed that compound 13d exhibited high potency against 3CLpro and helicase, with docking scores of -10.9 and -10.5 kcal/mol, respectively. Compound 10c showed su-perior docking scores against RBD and ACE2, with values of -8.7 and -11.8 kcal/mol, respectively. Compounds 10a, 13c, and 7b demonstrated excellent docking scores against RdRp, PLpro, and NRP-1, with values of -10.3, -10.4, and -8.6 kcal/mol, respectively.
Conclusion
The authors recommend further experimental assessments of compounds 13d, 10c, 10a, 13c, and 7b against SARS-CoV-2 multi-targets, considering their promising docking scores.
