Design, Synthesis and Evaluation of Some Novel1, 4-Naphthoquinone Derivatives to TreatCancer (original) (raw)
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Synthesis and Anti-HIV Activity of 4-(Naphthalen-1-yl)-1,2,5-thiadiazol-3- hydroxyl Derivatives
Chemical Biology & Drug Design, 2014
A series of 4-(naphthalen-1-yl)-1,2,5-thiadiazol-3hydroxyl derivatives (Ia-Im and IIa-IIe) designed as novel HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs) was synthesized via an expeditious route and evaluated for their anti-HIV activities in MT-4 cell cultures. All the synthesized compounds were structurally confirmed by spectral analyses. Biological results showed that three analogues displayed moderate inhibitory activity against wild-type (wt) HIV-1 replication with EC 50 values ranging from 16 to 22 lM. Molecular docking of compound Ih with wt HIV-1 RT was performed to understand the binding mode between these inhibitors and the wt HIV-1 RT and to rationalize some SARs.
Indian Journal of Pharmaceutical Education and Research, 2018
Objective: In the present study, a series of nineteen compound of 1-phenyl-3-(5-phenyl-1H-imidazol-1-yl) thiourea derivatives (5a-9b) were designed, synthesized, characterized by physicochemical and spectral data (IR, 1H NMR, and mass spectroscopy) and evaluated for their Anti-HIV activity with the aim to develop novel substituted imidazole derivatives with broad-spectrum chemotherapeutic properties. Methods: Compounds (5a-9b) were designed by using Glide 5.0 to carry out binding mode analysis of N-substituted imidazoles against reverse transcriptase enzyme of wild type as well as resistant strains of HIV-1 virus with PDB ID: 1RT2, synthesized by reacting various substituted anilines and substituted phenacyl bromides in four steps and evaluated their anti HIV activity as well as cytotoxicity assay through MTT colorimetric measure. Results: Compounds 6a, 6b, 6c, 6d, 7c, 9a and 9b being the most active exhibited therapeutic index that were >22.4, 31.1, 30.5, 51.5, 34.6, 30.5 and 85.6 compared to Zidovudine (AZT) having therapeutic index (TI) 514342.6. Compound 9b showed the highest docking score-12.47 in the active site of the HIV protein of 1RT2 as well better in vitro anti-HIV activity.
European Journal of Medicinal Chemistry, 2009
A series of 2-(4-(naphthalen-2-yl)-1,2,3-thiadiazol-5-ylthio)acetamide (TTA) derivatives were synthesized and evaluated as potent inhibitors of HIV-1. Among the newly disclosed TTAs, compounds 7f, 7g and 7c were the most potent inhibitors of HIV-1 replication of the series (EC 50 ¼ 0.17 AE 0.02, 0.36 AE 0.19 and 0.39 AE 0.05 mM, respectively), coupled with a reasonable selectivity index (SI > 1452, >845, and >774, respectively). They possess improved or similar HIV-1 inhibitory activity compared with NVP (EC 50 ¼ 0.208 mM) and DLV (EC 50 ¼ 0.320 mM). The preliminary structure-activity relationships among the newly synthesized congeners are discussed briefly and rationalized by docking studies.
Organic Communications, 2020
Quinones, especially 1,4-naphthoquinones, are one of the most significant and widely distributed phytochemical groups in nature. 1,4-Naphthoquinones and their synthetic derivatives are found to possess remarkable cytotoxic activities. In this study, a series of 2-aminonaphtho[2,3-d][1,3]thiazole-4,9-dione derivatives were synthesized and their structures were verified with spectral analysis. In vitro cytotoxic activities of the synthesized compounds were evaluated by using MTT assay against MKN-45 (Human Gastric cancer), MDA-MB-231 (Human Breast cancer) and HeLa (Human Cervical cancer) cell lines. Among the synthesized compounds, 3d inhibited MDA-MB-cell proliferation with an IC50 value of 0.276 µM. Compound 3a inhibited HeLa and MKN-45 cell proliferation with IC50 values of 0.336 µM and 8.769 µM, respectively. Compound 3b inhibited HELA cell proliferation with an IC50 value of 0.269 µM. Molecular docking results suggest that the ligands may bind to the hDNA TopoIIβ binding pocket a...
Synthesis and biological evaluation of 2-chloro-3-[(thiazol-2-yl)amino]-1,4-naphthoquinones
Bioorganic & Medicinal Chemistry Letters, 2019
A series of novel, substituted 2-chloro-3-[(thiazol-2-yl)amino]-1,4-naphthoquinones have been prepared and shown to exhibit promising concentration-dependent activity against human SH-SY5Y cells, Plasmodium falciparum, Mycobacterium tuberculosis and P. aeruginosa. Substituent effects on observed bioactivity have been explored; the para-fluorophenyl derivative 3d exhibited activity across the range of the bioassays employed, indicating the potential of the 2-chloro-3-[(4arylthiazol-2-yl)amino]-1,4-naphthoquinone scaffold in the development of novel, broad spectrum therapeutics.
Chemical Technology, 2012
The synthesis of new aminothiazole derivatives on the basis of substituted 1,4-naphthoquinones was carried out by the interaction of 2-R-3,6-dichloro-7-acylamino-1,4-naphthoquinones and potassium thiocyanate, 3,6-dichloro-2,7-diacylamino-1,4naphthoquinone and dithiocyanate, of 2-R-3,6-dichloro-7-amino-1,4-naphthoquinones, 2-amino-7-nitro-3,6-dichloro-1,4naphthoquinone and thiourea with the subsequent cyclization in aminothiazoles of 1,4-naphthoquinone. The physical and chemical properties of these compounds were determined, and the methods of their preparation are presented. The PASS computer program was used to predict the biological activity spectra of the new 1,4-naphthoquinone aminothiazole derivatives and to determine the most promising biological activities for experimental testing. Antibacterial and fungicidal activities were studied using the cultures of Staphylococcus aureus, Escherichia coli and Candida tenuis microorganisms. Some of the study compounds were found to have a moderate antibacterial and fungicidal activity, which in more than 90 % of cases coincided with the computational predictions. The analysis of the structureantimicrobial activity relationships provides recommendations for the design of the new derivatives. Some other biological activities have been predicted by PASS for these compounds, including antiviral, antineoplastic, immunomodulating, acute neurological disease treatment, antiparkinsonian, etc., which help to identify areas for the further research. Thus, the 1,4-naphthoquinone aminothiazole derivatives have been shown to be a promising class for the preparation of novel pharmacological agents with different applications.
Journal of Heterocyclic Chemistry, 2010
in Wiley InterScience (www.interscience.wiley.com). Naphthoquinones undergo 1,3-dipolar cycloaddition with bicyclic münchnones generated from thiazolidines affording new pyrrolo-thiazoles with a fused quinone nucleus. The products were obtained as single enantiomers in good yields. These benzo[f]thiazolo[4,3-a]isoindole-6,11(1H,3H)-diones are comprised of four fused rings and present a very planar structure. The evaluation of their anticancer activity against melanoma A375 and colorectal adenocarcinoma WiDr human cell lines showed only moderate activity but gave insight into the modeling of new structures. [Color figure can be viewed in the online issue, which is available at www.interscience.wiley.com.\] J. Heterocyclic Chem., 47, 960 (2010).
Archiv der Pharmazie, 2008
A series of novel 2,4-disubstituted 7-methyl-1,1,3-trioxo-2,4-dihydro-pyrazolo[4,5-e] [1,2,4]thiadiazines (PTDs) was synthesized, structurally confirmed by spectral analysis, and evaluated for their anti-HIV activities by inhibition of HIV-induced cytopathogenicity in MT-4 cell culture. The results showed that some compounds exhibited inhibitory activity specifically against HIV-2 replication. The most active HIV-2 inhibitor was compound 7i (R 1 = benzyl, R 2 = 4-t-butyl-benzyl) with an EC 50 value of 18.7 lM and SI=15, which may provide a useful lead for further molecular optimization.