A novel approach towards design, synthesis and evaluation of some Schiff base analogues of 2-aminopyridine and 2-aminobezothiazole against hepatocellular carcinoma

Chacko, Shinu; Samanta, Subir

doi:10.1016/j.biopha.2017.01.108

Cited by 30 publications

(14 citation statements)

References 42 publications

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“…Both histology and SEM analyses revealed that degenerated tumor cells, loss of architecture and tumoral vacuoles were formed in NDEA-induced rats as previously reported. 9 The histological investigation of the rats treated with 4A , 6A and 5-FU showed cells with architecture more or less similar to control (group I), representing the hepatoprotective activity of the compounds in cancerous condition. In the SEM analysis, we also observed degenerated necrotic tissues in carcinogen-exposed rats, which were regularized to a great extent in 4A and 6A treatment groups.…”

Section: Discussionmentioning

confidence: 85%

“…The worldwide mortality rate of all other leading cancers (such as lung, breast and prostate cancers) is declining, whereas the death rate of liver cancer is increased by 2.8% in men and 3.4% in women each year. 8 , 9 Approximately 748,000 new cases (9.2% of all new global cancer cases) of HCC are being diagnosed every year worldwide. 10 …”

Section: Introductionmentioning

confidence: 99%

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5H-benzo[h]thiazolo[2,3-b]quinazolines ameliorate NDEA-induced hepatocellular carcinogenesis in rats through IL-6 downregulation along with oxidative and metabolic stress reduction

Keshari

Singh

Kumar

et al. 2017

DDDT

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5H-benzo[h]thiazolo[2,3-b]quinazoline scaffold is known to have an antitumor effect on certain types of malignancies; however, its effect on hepatocellular carcinoma (HCC) remains unclear. Previously, we reported p-toluenesulfonic acid-promoted syntheses, molecular modeling and in vitro antitumor activity of 5H-benzo[h]thiazolo[2,3-b]quinazoline against human hepatoma (Hep-G2) cells where compounds 4A and 6A were found to be potent inhibitors among the series. In continuation to our previous effort to develop novel therapeutic strategies for HCC treatment, here we investigated the in vivo antitumor activity and the mechanism underlying the effects of 4A and 6A in N-nitrosodiethylamine (NDEA)-induced HCC using male Wistar rats. NDEA was administered weekly intraperitoneally at a dose of 100 mg/kg for 6 weeks. Various physiological and morphological changes, oxidative parameters, liver marker enzymes and cytokines were assessed to evaluate the antitumor effect of 4A and 6A. In addition, proton nuclear magnetic resonance-based serum metabolomics were performed to analyze the effects of 4A and 6A against HCC-induced metabolic alterations. Significant tumor incidences with an imbalance in carcinogen metabolizing enzymes and cellular redox status were observed in carcinogenic rats. Tumor inhibitory effects of 4A and 6A were noted by histopathology and biochemical profiles in NDEA-induced hepatic cancer. Compounds 4A and 6A had a potential role in normalizing the elevated levels of inflammatory mediators such as interleukin-1β (IL-1β), IL-2, IL-6 and IL-10. At molecular level, the real-time quantitative reverse-transcribed polymerase chain reaction analysis revealed that 4A and 6A attenuated the IL-6 gene overexpression in hepatic cancer. Further, orthogonal partial least squares discriminant analysis scores plot demonstrated a significant separation of 4A and 6A-treated groups from carcinogen control group. Both the compounds have potential to restore the imbalanced metabolites due to HCC, signifying promising hepatoprotective activities. All these findings suggested that 4A and 6A could be potential drug candidates to treat HCC.

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Section: Discussionmentioning

confidence: 85%

Section: Introductionmentioning

confidence: 99%

5H-benzo[h]thiazolo[2,3-b]quinazolines ameliorate NDEA-induced hepatocellular carcinogenesis in rats through IL-6 downregulation along with oxidative and metabolic stress reduction

Keshari

Singh

Kumar

et al. 2017

DDDT

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“…The drugs should be orally absorbed and distributed to the site of action and eliminated from the body without leaving any traces, which produces adverse effects. Hence, the tools and computer-aided methods, nowadays, have become popular in identifying good drug candidate molecule [ 21 , 22 , 23 ].…”

Section: Methodsmentioning

confidence: 99%

Druggability and Binding Site Interaction Studies of Potential Metabolites Isolated from Marine Sponge Aurora globostellata against Human Epidermal Growth Factor Receptor-2

Sugappriya

Dorairaj²,

Bhaskaran

et al. 2017

Bioinformation

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To study the involvement of compounds stigmasterol and oleic acid isolated from marine sponge Aurora globostellata and docking against the Human Epidermal Growth Factor Receptor-2 in breast cancer. The comparative molecular docking was performed with the natural compounds from marine sponge and the synthetic drugs used in breast cancer treatment against the target HER2. The molecular docking analysis was done using GLIDE in Schrodinger software package. The ADME properties were calculated using the Qikprop. The observation of the common binding site for all the ligands confirms the binding pocket; where the isolated compound Stigmasterol agrees well with the binding residues and thus can be optimized further to arrive at a molecule that has a high binding affinity and low binding constant. The results of the docking studies carried out on HER2 provide an insight for the compound stigmasterol to have drug like properties than oleic acid. These results are supportive to confirm the marine sponges as a better lead for cancer therapeutics.

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“…b) Modulation of the length of the linker between the amide and R groups, from 0 to 4 methylenes (carbon atoms), with the aim of finding the optimal chain length required for activity. c) Several heterocycles (mono-and bi-cyclic) with proven cytotoxic effects, such as 2-aminothiazole [29,30], aminoquinoline [31][32][33] and 2-aminobenzothiazole [34,35], which also have antioxidant capacity [36]. d) Alkyl, cycloalkyl and hydroxyalkyl chains in order to modulate the lipophilicity along with the entropy of the molecules.…”

Section: A N U S C R I P Tmentioning

confidence: 99%

Novel selenadiazole derivatives as selective antitumor and radical scavenging agents

Ruberte

Plano

Encı́o

et al. 2018

European Journal of Medicinal Chemistry

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Twenty-seven novel benzo[c][1,2,5]selenadiazole-5-carboxylic acid (BSCA) derivatives were designed and synthesized. Anti-proliferative activity of these structures was tested in vitro against a panel of five human cancer cell lines, including prostate (PC-3), colon (HT-29), leukemia (CCRF-CEM), lung (HTB-54) and breast (MCF-7). Four compounds (5, 6, 7 and 19) showed potent inhibitory activity with GI values below 10 μM in at least one of the cancer cell lines. The selectivity of these compounds was further examined in two non-malignant cell lines derived from breast (184B5) and lung (BEAS-2B). Compound 7 exhibited promising anti-proliferative activity (GI = 3.7 μM) in MCF-7 cells, together with high selectivity index (SI > 27.1). The induction of cell death by compound 7 was independent of the apoptotic process and it did not affect cell cycle progression either. Likewise, radical scavenging properties of the new selenadiazole derivatives were confirmed by testing their ability to scavenge DPPH radicals. Four compounds (1, 2, 8 and 9) showed potent radical scavenging activity, compound 9 being the most effective. Overall, while compound 7 was identified as the most cell growth inhibitory agent and selectively toxic to cancer cells, compound 9 proved to be the most potent antioxidant among the selenadiazole derivatives synthesized. This series of compounds can serve as an excellent scaffold to achieve new and potent antioxidant compounds useful for several diseases, i.e. cancer, neurodegenerative, heart diseases and leishmaniasis, considering the high radical scavenging activity and low toxicity showed by most of the compounds.

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A novel approach towards design, synthesis and evaluation of some Schiff base analogues of 2-aminopyridine and 2-aminobezothiazole against hepatocellular carcinoma

Cited by 30 publications

References 42 publications

5H-benzo[h]thiazolo[2,3-b]quinazolines ameliorate NDEA-induced hepatocellular carcinogenesis in rats through IL-6 downregulation along with oxidative and metabolic stress reduction

5H-benzo[h]thiazolo[2,3-b]quinazolines ameliorate NDEA-induced hepatocellular carcinogenesis in rats through IL-6 downregulation along with oxidative and metabolic stress reduction

Druggability and Binding Site Interaction Studies of Potential Metabolites Isolated from Marine Sponge Aurora globostellata against Human Epidermal Growth Factor Receptor-2

Novel selenadiazole derivatives as selective antitumor and radical scavenging agents

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