Synthesis and SAR studies of potent H+/K+-ATPase and anti-inflammatory activities of symmetrical and unsymmetrical urea analogues

Rakesh, K.P.; Darshini, N.; Vidhya, S.; Rajesha,; Mallesha, N.

doi:10.1007/s00044-017-1878-x

Cited by 13 publications

(6 citation statements)

References 22 publications

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“…In addition to the feasibility of supra-molecular interactions, all of these four molecules manifest much significance regarding their biological activities from a pharmaceutical point of view. Further, their metabolism in the body does not result in toxic metabolites so, this selection of co-formers is not only safe for in-vivo administration but can also be helpful in the improvement of 5-FU pharmacological properties (Langley and Rothwell, 2012, Li, 2017, Rakesh, 2017). The major elements in all the selected co-formers like F, S, O, N and H are among the top ten elements in approved drugs (Fang, 2019).…”

Section: Introductionmentioning

confidence: 99%

Green synthesis and biological evaluation of novel 5-fluorouracil derivatives as potent anticancer agents

Jubeen

Liaqat

Sultan

et al. 2019

Saudi Pharmaceutical Journal

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This study reports the formation of 5-FU co-crystals with four different pharmacologically safe co-formers; Urea, Thiourea, Acetanilide and Aspirin using methanol as a solvent. Two fabrication schemes were followed i.e., solid-state grinding protocol, in which API and co-formers were mixed through vigorous grinding while in the other method separate solutions of both the components were made and mixed together. The adopted approaches offer easy fabrication protocols, no temperature maintenance requirements, no need of expensive solvents, hardly available apparatus, isolation and purification of the desired products. In addition, there is no byproducts formation, In fact, a phenomenon embracing the requirements of green synthesis. Through FTIR analysis; for API the N—H absorption frequency was recorded at 3409.02 cm−1 and that of —CO was observed at 1647.77 cm−1. These characteristics peaks of 5-FU were significantly shifted and recorded at 3499.40 cm−1 and 1649.62 cm−1 for 5-FU-Ac (3B) and 3496.39 cm−1 and 1659.30 cm−1 for 5-FU-As (4B) co-crystals for N—H and —CO groups respectively. The structural differences between API and co-crystals were further confirmed through PXRD analysis. The characteristic peak of 5-FU at 2θ = 28.79918o was significantly shifted in the graphs of co-crystals not only in position but also with respect to intensity and FWHM values. In addition, new peaks were also recorded in all the spectra of co-formers confirming the structural differences between API and co-formers. In addition, percent growth inhibition was also observed by all the co-crystals through MTT assay against HCT 116 colorectal cell lines in vitro. At four different concentrations; 25, 50, 100 and 200 µg/mL, slightly different trends of the effectiveness of API and co-crystals were observed. However; among all the co-crystal forms, 5-FU-thiourea co-crystals obtained through solution method (2B) proved to be the most effective growth inhibitor at all the four above mentioned concentrations.

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Section: Introductionmentioning

confidence: 99%

Green synthesis and biological evaluation of novel 5-fluorouracil derivatives as potent anticancer agents

Jubeen

Liaqat

Sultan

et al. 2019

Saudi Pharmaceutical Journal

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“…Rakesh et al (2017) studied a series of disubstituted ureas for their in vitro H + /K + ATPase (proton pump) and anti-inflammatory activity. Diarylurea 35 behaved as an antiulcer, exhibiting higher activity against proton pump than omeprazole (IC 50 = 18.4 µg/mL versus 38.2 µg/mL), while compound 36 displayed higher anti-inflammatory activity than indomethacin (IC 50 = 20.3 µg/mL versus 44.8 µg/mL) [ 81 ].…”

Section: Diarylureas As Anti-inflammatory Agents and Antiulcer Agementioning

confidence: 99%

Diarylureas: Repositioning from Antitumor to Antimicrobials or Multi-Target Agents against New Pandemics

et al. 2021

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Antimicrobials have allowed medical advancements over several decades. However, the continuous emergence of antimicrobial resistance restricts efficacy in treating infectious diseases. In this context, the drug repositioning of already known biological active compounds to antimicrobials could represent a useful strategy. In 2002 and 2003, the SARS-CoV pandemic immobilized the Far East regions. However, the drug discovery attempts to study the virus have stopped after the crisis declined. Today’s COVID-19 pandemic could probably have been avoided if those efforts against SARS-CoV had continued. Recently, a new coronavirus variant was identified in the UK. Because of this, the search for safe and potent antimicrobials and antivirals is urgent. Apart from antiviral treatment for severe cases of COVID-19, many patients with mild disease without pneumonia or moderate disease with pneumonia have received different classes of antibiotics. Diarylureas are tyrosine kinase inhibitors well known in the art as anticancer agents, which might be useful tools for a reposition as antimicrobials. The first to come onto the market as anticancer was sorafenib, followed by some other active molecules. For this interesting class of organic compounds antimicrobial, antiviral, antithrombotic, antimalarial, and anti-inflammatory properties have been reported in the literature. These numerous properties make these compounds interesting for a new possible pandemic considering that, as well as for other viral infections also for CoVID-19, a multitarget therapeutic strategy could be favorable. This review is meant to be an overview on diarylureas, focusing on their biological activities, not dwelling on the already known antitumor activity. Quite a lot of papers present in the literature underline and highlight the importance of these molecules as versatile scaffolds for the development of new and promising antimicrobials and multitarget agents against new pandemic events.

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“…Other various types of ulcer include acute and chronic ulcer (Rakesh et al, 2017), and can be ascribed to imbalances between aggressive factors such as acid and pepsin, and protective factors such as bicarbonates, blood flow and mucous membrane, in the stomach. This balance may be disturbed due to Helicobacter pyroli infection (Skoglung, 2008;Rakesh et al, 2017;Wang et al, 2017), a gram-negative bacteria parasite, which has successfully colonized more than half of human population, and caused about 15-20% of pathologies such as adenocarcinomas, duodenal ulcer, and stomach lymphomas (Shi et al, 2016). Pain-killer drugs, such as ibuprofen, naproxen and diclofenac, which contain carboxylic groups are also believed to cause about 40% of peptic ulcer diseases (Fashner and Gitu, 2015;Shamsudeen et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

“…H + /K + -ATPase is a member of the class 2C P-type ion-transport ATPases. Also known as the primary gastric proton pump, which moves acid across parietal cells, and gastric mucosa (Rakesh et al, 2017). It was reported that H + /K + -ATPase (gastric proton/potassium pump) is the last passage of gastric acid secretion, and hypersecretion of this acid result in severe superior gastrointestinal bleeding (Wang et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

“…Excess use of pain-killer drugs can cause mucosal injury, inflammation, intestinal permeability, protein loss, with a severe complication like anemia, obstruction diverticulum, ileal dysfunction and diaphgram structures (Utzeri & Usai, 2017). Therefore, in other to narrow the aforementioned problems, demand in search and design of novel compounds possessing anti-ulcer, and inflammation action with an improved profile is still a necessity (Rakesh et al, 2017;Mabeka, 2017).…”

Section: Introductionmentioning

confidence: 99%

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Molecular Docking and Quantitative Structure-Activity Relationship (Qsar) Studies of Some Selected Anti-Ulcer Inhibitors

2019

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Proton pump inhibitors portray the first choice for treating various ulcer disease, because they inhibis H + /K +-ATpase enzyme by covalently binding to a cysteine residue of either potassium or proton pump. Therefore, this enzyme is a validated target for anti-ulcer remedy/drugs. A quantitative structure-activity relationship and molecular docking studies have been made on 30 benzo[d]thiazole series as H + /K +-ATPase inhibitors. Density Functional Theory was used to optimize the geometry of the anti-ulcer compounds. Four types of molecular descriptors were generated in other to know the relationship that exit between anti-ulcer activity and structural properties of these compounds. The QSAR result revealed high statistically significant correlation coefficients R 2 = 0.9401, R 2 adj = 0.9250, Q 2 LOO = 0.8842 and R 2 pred= 0.7975. Our QSAR model showed an excellent predictive activity with the chemical properties of the compounds. The results of the docking analysis revealed that most of the compounds showed a very good relationship with the active receptor, with a better docking score of-9.1kcal/mol. The physicochemical parameters are to be considered when improving the inhibitory activities of benzo[d]thiazole against the enzyme that causes the ulcer

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Synthesis and SAR studies of potent H+/K+-ATPase and anti-inflammatory activities of symmetrical and unsymmetrical urea analogues

Cited by 13 publications

References 22 publications

Green synthesis and biological evaluation of novel 5-fluorouracil derivatives as potent anticancer agents

Green synthesis and biological evaluation of novel 5-fluorouracil derivatives as potent anticancer agents

Diarylureas: Repositioning from Antitumor to Antimicrobials or Multi-Target Agents against New Pandemics

Molecular Docking and Quantitative Structure-Activity Relationship (Qsar) Studies of Some Selected Anti-Ulcer Inhibitors

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