Discovery of Novel Tricyclic Thiazepine Derivatives as Anti-Drug-Resistant Cancer Agents by Combining Diversity-Oriented Synthesis and Converging Screening Approach

Xiang, Jinbao; Zhang, Zhuoqi; Mu, Yan; Xu, Xianxiu; Guo, Sigen; Liu, Yong-Jin; Russo, Daniel P.; Zhu, Hao; Yan, Bing; Bai, Xu

doi:10.1021/acscombsci.6b00010

Cited by 23 publications

(9 citation statements)

References 44 publications

(42 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…On similar lines, tricyclic derivatives are reported in multitude of conditions ranging from allergy, viral infections, central nervous system pathologies, inflammation, cancer to cardiovascular diseases 42 , 43 . Their role in the prevention of multi drug resistant cancer has recently been studied 44 . The stability of the protein-compound complexes were found to be stabilized by non-covalent interactions such as hydrogen bonding, Van der Waal and electrostatic.…”

Section: Discussionmentioning

confidence: 99%

Identification of new inhibitors against human Great wall kinase using in silico approaches

Ammarah

Kumar

Pal

et al. 2018

Sci Rep

View full text Add to dashboard Cite

Microtubule associated serine/threonine kinase (MASTL) is an important Ser/Thr kinase belonging to the family of AGC kinases. It is the human orthologue of Greatwall kinase (Gwl) that plays a significant role in mitotic progression and cell cycle regulation. Upregulation of MASTL in various cancers and its association with poor patient survival establishes it as an important drug target in cancer therapy. Nevertheless, the target remains unexplored with the paucity of studies focused on identification of inhibitors against MASTL, which emphasizes the relevance of our present study. We explored various drug databases and performed virtual screening of compounds from both natural and synthetic sources. A list of promising compounds displaying high binding characteristics towards MASTL protein is reported. Among the natural compounds, we found a 6-hydroxynaphthalene derivative ZINC85597499 to display best binding energy value of −9.32 kcal/mol. While among synthetic compounds, a thieno-pyrimidinone based tricyclic derivative ZINC53845290 compound exhibited best binding affinity of value −7.85 kcal/mol. MASTL interactions with these two compounds were further explored using molecular dynamics simulations. Altogether, this study identifies potential inhibitors of human Gwl kinase from both natural and synthetic origin and calls for studying these compounds as potential drugs for cancer therapy.

show abstract

Section: Discussionmentioning

confidence: 99%

Identification of new inhibitors against human Great wall kinase using in silico approaches

Ammarah

Kumar

Pal

et al. 2018

Sci Rep

View full text Add to dashboard Cite

show abstract

“…291,292 These molecules have found their place as anticancer candidates and are being developed by various organic and medicinal chemists to aid to the future field of cancer chemotherapy. 293,294 Also, various tricyclic antidepressants like clomipramine has also shown to display antitumor profile in a study carried out by Palmerton et al 295 Hence, various thiazepines and benzothiazepines can aid to the future field of cancer chemotherapeutics.…”

Section: Thiolactamsmentioning

confidence: 99%

“…Various synthetic methods have been developed to procure thiazepines and benzothiazepines over the past years and new approaches continue to emerge, owing to their importance as intermediates for synthesizing various biologically important derivatives 291,292 . These molecules have found their place as anticancer candidates and are being developed by various organic and medicinal chemists to aid to the future field of cancer chemotherapy 293,294 . Also, various tricyclic antidepressants like clomipramine has also shown to display antitumor profile in a study carried out by Palmerton et al 295 Hence, various thiazepines and benzothiazepines can aid to the future field of cancer chemotherapeutics.…”

Section: Introductionmentioning

confidence: 99%

Expedition of sulfur‐containing heterocyclic derivatives as cytotoxic agents in medicinal chemistry: A decade update

Laxmikeshav

Kumari

Shankaraiah

2021

Medicinal Research Reviews

View full text Add to dashboard Cite

This review article proposes a comprehensive report of the design strategies engaged in the development of various sulfur-bearing cytotoxic agents. The outcomes of various studies depict that the sulfur heterocyclic framework is a fundamental structure in diverse synthetic analogs representing a myriad scope of therapeutic activities. A number of five-, six-and seven-membered sulfur-containing heterocyclic scaffolds, such as thiazoles, thiadiazoles, thiazolidinediones, thiophenes, thiopyrans, benzothiazoles, benzothiophenes, thienopyrimidines, simple and modified phenothiazines, and thiazepines have been discussed. The subsequent studies of the derivatives unveiled their cytotoxic effects through multiple mechanisms (viz. inhibition of tyrosine kinases, topoisomerase I and II, tubulin, COX, DNA synthesis, and PI3K/Akt and Raf/MEK/ERK signaling pathways), and several others. Thus, our concise illustration explains the design strategy and anticancer potential of these five-and six-membered sulfur-containing heterocyclic molecules along with a brief outline on seven-membered sulfur heterocycles. The thorough assessment of antiproliferative activities with the reference drug allows a proficient assessment of the structure-activity relationships (SARs) of the diversely synthesized molecules of the series.

show abstract

“…Benzothiazepines have been identified as calcium antagonists, leading to the development of Diltiazem for the treatment of diseases such as high blood pressure or angina [48]. Meanwhile, dibenzothiazepines have been widely used for antipsychotic drugs, such as quetiapine [49] or clothiapine [50], and tricyclic benzothiazepines have been identified as potential anti-drug-resistant cancer agents [51]. Despite their importance, most processes for their synthesis require harsh conditions, expensive reagents, high catalyst loading, corrosive or toxic reagents, and often lead to several side reactions [52].…”

Section: Of 35mentioning

confidence: 99%

Ultrasound for Drug Synthesis: A Green Approach

2020

View full text Add to dashboard Cite

This last century, the development of new medicinal molecules represents a real breakthrough in terms of humans and animal life expectancy and quality of life. However, this success is tainted by negative environmental consequences. Indeed, the synthesis of drug candidates requires the use of many chemicals, solvents, and processes that are very hazardous, toxic, energy consuming, expensive, and generates a large amount of waste. Many large pharmaceutical companies have thus moved to using green chemistry practices for drug discovery, development, and manufacturing. One of them is the use of energy-efficient activation techniques, such as ultrasound. This review summarizes the latest most representative works published on the use of ultrasound for sustainable bioactive molecules synthesis.

show abstract

Discovery of Novel Tricyclic Thiazepine Derivatives as Anti-Drug-Resistant Cancer Agents by Combining Diversity-Oriented Synthesis and Converging Screening Approach

Cited by 23 publications

References 44 publications

Identification of new inhibitors against human Great wall kinase using in silico approaches

Identification of new inhibitors against human Great wall kinase using in silico approaches

Expedition of sulfur‐containing heterocyclic derivatives as cytotoxic agents in medicinal chemistry: A decade update

Ultrasound for Drug Synthesis: A Green Approach

Contact Info

Product

Resources

About