Synthesis and antitumor potential of new 7-halocoumarin-4-acetic acid derivatives

Citrullus lanatus is a fruit that is eaten and carries many by-products like rind and seeds that are abandoned and fed to animals. Numerous studies have demonstrated the bio-medical properties of Citrullus lanatus by-products, making it a superior choice of natural source for medicinal products. Citrullus lanatus by-products' medical properties are due to their pharmacological significance, related to the availability of essential phytochemicals such as saponin, alkaloids, fatty acids, phenolic, citrulline, lycopene, coumarin, minerals, and other natural products. Gastrointestinal ulceration, diabetes, hypertension, cardiovascular disorders, and many kinds of malignancies have been treated with these by-products extract. The following review aimed to provide a thorough summary of the advantages of Citrullus lanatus byproducts in the management of different ailments.

Section: Anticancer Propertymentioning

confidence: 99%

Untitled

2022

“…The reaction mass was chilled for 36 h before being filtered through an ice-water mixture. The raw was purified from impurities by recrystallizing ethyl acetate [37].…”

Section: Synthetic Skeletal Pathwaymentioning

confidence: 99%

Untitled

2022

The incidence of many human disorders, such as cancer, oxidative stress, diabetes mellitus, and inflammatory diseases, has been mountingly increased because of many factors, including environmental pollution, static lifestyle, and unhealthy feeding. In an attempt to explore a scaffold with multiple biomedical activities, four natural phenolic acids, namely vanillic-, protocatechuic-, ferulic-, and caffeic-acid, were selected to construct twelve derived coumarins. The skeletal formulas of the semi-synthesized coumarins were confirmed by analyzing their spectra afforded via various spectrophotometers. The biomedical characteristics of these coumarins were investigated and included their antioxidant, anti-inflammatory, antidiabetic, and anticancer activities. The antioxidant activity was quantified by monitoring the potential of these coumarins to reduce DPPH and hydroxyl oxidants and provide an electron in the redox reaction. The anti-inflammatory activity was detected by specifying the inhibitory and selectivity of these coumarins on two COX isozymes. The antidiabetic activity was determined by examining the capacity of these coumarins to suppress two enzymes involved in blood glucose regulation. The anticancer activity and cytotoxicity were examined via MTT-based methodology versus four cancer cell lines and one normal cell line. The findings revealed that the semi-synthesized coumarins exhibited potent antioxidant and anticancer activities with low-induced cytotoxicity. Also, these coumarins showed modest antidiabetic potential and inhibitory effects versus the COX isozymes, with some selectivity toward the inhibition of COX-2. The authors concluded that these coumarins, specifically YC11, provide a valid structural template for synthesizing multi-functional agents effective in treating health situations in which oxidative stress, inflammation, diabetes, and cancer are combined.

“…Finally, the poor penetration across the bloodbrain barrier (except for SA0) might mean that these compounds will have low toxicity as a result of a lack of neurological side effects. This limited number of adverse effects is critical in determining CNS toxicity [56].…”

Section: Theoretical Pharmacokinetic Parametersmentioning

confidence: 99%

Untitled

2022

This work involves the synthesis of eight novel fused coumarin compounds, which were confirmed by various spectrophotometers and then, assessed for their apoptotic-inducing and free radical-quenching activities. The pharmacokinetic parameters were evaluated in silico using pre-ADMET, a free online program. The apoptotic-inducing activity was tested against six tumorigenic cell lines. Also, their safety against normal cells was examined. The free radical-quenching activity was assessed by checking these compounds' ability to eliminate DDPT and hydroxyl moieties. Pharmacokinetic investigations showed that the synthesized fused coumarin compounds have excellent penetration across the GIT mucosa and most of them have poor penetration across the blood-brain barrier. These findings suggest good oral bioavailability along with low neurological toxicity profiles. The evaluation of the apoptotic-inducing activity revealed that all of the compounds have weaker activity as compared to the reference. Among these compounds, SA4 was the most potent one. Nevertheless, all of these new compounds had an excellent safety profile against normal cells. On the other hand, the assessment of the free radical-quenching activity of these synthesized compounds also indicated that all of them were less active than the reference. In this field, SA0 was the strongest free radical-quenching compound. From these realizations, along with the apparent safety and good pharmacokinetic characteristics in accordance with the in silico study, compounds SA4 and SA0 are considered the most promising agents. The authors hope that these new fused coumarin compounds can be utilized in the coming years for the production of new powerful drugs with apoptoticinducing and free radical-quenching potentials which can help in the battle against many diseases.