Development of spiro-3-indolin-2-one containing compounds of antiproliferative and anti-SARS-CoV-2 properties

Abstract: A series of 1″-(alkylsulfonyl)-dispiro[indoline-3,2′-pyrrolidine-3′,3″-piperidine]-2,4″-diones 6a‒o has been synthesized through regioselective multi-component azomethine dipolar cycloaddition reaction of 1-(alkylsulfonyl)-3,5-bis(ylidene)-piperidin-4-ones 3a‒h. X-ray diffraction studies (6b‒d, h) confirmed the structures. The majority of the synthesized analogs reveal promising antiproliferation properties against a variety of human cancer cell lines (MCF7, HCT116, A431 and PaCa2) with good selectivity index towards normal cell (RPE1). Some of the synthesized agents exhibit potent inhibitory properties against the tested cell lines with higher efficacies than the standard references (sunitinib and 5-fluorouracil). Compound 6m is the most potent. Multi-targeted inhibitory properties against EGFR and VEGFR-2 have been observed for the synthesized agents. Flow cytometry supports the antiproliferation properties and shows the tested agents as apoptosis and necrosis forming. Vero cell viral infection model demonstrates the anti-SARS-CoV-2 properties of the synthesized agents. Compound 6f is the most promising (about 3.3 and 4.8 times the potency of the standard references, chloroquine and hydroxychloroquine). QSAR models explain and support the observed biological properties

IN VITRO ALPHA-GLUCOSIDASE INHIBITORY ACTIVITY OF EGYPTIAN PLANT EXTRACTS AS AN INDICATION FOR THEIR ANTIDIABETIC ACTIVITY

Objective: Diabetes mellitus is a highly prevalent chronic disease in Egypt leading to high socioeconomic problems, especially in the cities due to the unhealthy life style. Although many drugs are available, they have many side effects. Furthermore, the body arouses resistance after a while for the drug so it should be changed every once in a while. Plants could be a good source for drugs. In Egypt, we have a rich flora which has not been subjected to systematic screening for antidiabetic activity.Methods: The aim of this work was to screen 264 plant extracts for their in vitro α-glucosidase inhibitory activity. Those extracts which gave more than 70% inhibition were screened on different concentrations and their inhibitory concentrations giving 50% activity (IC50) were calculated.Results: Out of all the tested extracts, 63 gave more than or equal 70% inhibition on α-glucosidase at the tested concentration (25 ppm). After the calculation of the IC50 values, 10 extracts were chosen for further study having 5 ppm and less IC50.Conclusion: The most active plant extract is Pinus roxburghii Sarg. branches (IC50 is 2.47 ppm)

Screening of natural products for therapeutic activity against solid tumors

258-264Most of the currently used cancer therapeutics are natural products. These agents were generally discovered based on their toxicity to tumour cells using various bioassays. Although the exact mechanisms of action of the most commonly used cancer therapeutics such as anthracyclins, podophyllotoxins and camptothecin are incompletely understood, it is becoming increasingly clear that these agents often show complex modes of action at the cellular level, interacting with numerous targets. Such complex modes of action may be the very reason for clinical efficacy. For discovering new cytotoxic anticancer drugs sophisticated screening methods were used. The principles of such screening projects conducted, using collections of purified natural products or extracts from plants have been described. By performing simple but robust pre-screening tests such as the brine shrimp assay, bioactive extracts can be identified. Extracts (65) prepared from a collection of Egyptian plants were identified that showed cytotoxity on HepG2 cells. Interestingly, 22 (33%) of these raw extracts, induced > 2-fold induction of caspase-cleavage activity in a colon carcinoma cell line, consistent with induction of apoptosis. Only a fraction of the diversity of the biosphere has been tested for biological activity and novel cancer therapeutics remains to be discovered

An Eco-Friendly Synthetic Approach for Copper Nanoclusters and Their Potential in Lead Ions Sensing and Biological Applications

A new preparation route for high-luminescent blue-emission pepsin copper nanoclusters (Pep-CuNCs) is introduced in this work. The synthesized nanoclusters are based on a pepsin molecule, which is a stomach enzyme that works to digest proteins that exist in undigested food. Here, we have developed an eco-friendly technique through microwave-assisted fast synthesis. The resulting copper nanoclusters (CuNCs) exhibit significant selectivity towards Pb(II) ions. The pepsin molecule was utilized as a stabilizer and reducing agent in the production procedure of Pep-CuNCs. The characteristics of the resulting Pep-CuNCs were studied in terms of size, surface modification, and composition using various sophisticated techniques. The CuNCs responded to Pb(II) ions through the fluorescence quenching mechanism of the CuNCs’ fluorescence. Thus, great selectivity of Pep-CuNCs towards Pb(II) ions was observed, allowing sensitive determination of this metal ion at lab-scale and in the environment. The CuNCs have detection limits for Pb(II) in very tenuous concentration at a nanomalar scale (11.54 nM). The resulting Pep-CuNCs were utilized significantly to detect Pb(II) ions in environmental samples. Additionally, the activity of Pep-CuNCs on different human tumor cell lines was investigated. The data for the observed behavior indicate that the Pep-CuNCs displayed their activity against cancer cells in a dose dependent manner against most utilized cancer cell lines

Anticancer evaluation and molecular modeling of multi-targeted kinase inhibitors based pyrido[2,3-d]pyrimidine scaffold

An efficient synthesis of substituted pyrido[2,3-d]pyrimidines was carried out and evaluated for in vitro anticancer activity against five cancer cell lines, namely hepatic cancer (HepG-2), prostate cancer (PC-3), colon cancer (HCT-116), breast cancer (MCF-7), and lung cancer (A-549) cell lines. Regarding HepG-2, PC-3, HCT-116 cancer cell lines, 7-(4-chlorophenyl)-2-(3-methyl-5-oxo-2,3-dihydro-1H-pyrazol-1-yl)-5-(p-tolyl)- pyrido[2,3-d]pyrimidin-4(3H)-one (5a) exhibited strong, more potent anticancer (IC50: 0.3, 6.6 and 7 µM) relative to the standard doxorubicin (IC50: 0.6, 6.8 and 12.8 µM), respectively. Kinase inhibitory assessment of 5a showed promising inhibitory activity against three kinases namely PDGFR β, EGFR, and CDK4/cyclin D1 at two concentrations 50 and 100 µM in single measurements. Further, a molecular docking study for compound 5a was performed to verify the binding mode towards the EGFR and CDK4/cyclin D1 kinases

Antioxidant potentials and inhibitory activities of α-amylase, α-glucosidase, and acetylcholinesterase of different fractions from Salsola tetragona Delile

ABSTRACTThe medicinal use of Salsola tetragona Delile (Amaranthaceae) aerial parts is a longstanding tradition. This study delved into the plant’s potential as an antioxidant, anti-diabetic, and anti-Alzheimer agent. The aerial portion extracted and evaluated four fractions (n-hexane, dichloromethane, ethyl acetate, n-butanol) for their antioxidant activity using DPPH, FRAP, and anti-hemolysis tests, as well as the inhibitory activity of cholinesterase and carbohydrate digesting enzymes. The results showed that the dichloromethane fraction (St.DCM) of S. tetragona had a significant ability to scavenge DPPH• radicals. The ethyl acetate fraction (St.EtOAc) had the best reduction power test activity compared to other solvent fractions. The n-hexane fraction (St.Hex) was most effective in the anti-hemolysis test. The ethyl acetate fraction also had inhibitory activities (p < .05) with IC50 values of 70 ± 1.80 µg/ml for α-glycosidase, equivalent to the n-butanol fraction (St.n-BuOH), which had very significant activity (p < .05) in the α-amylase inhibition test with an IC50 of 64 ± 1.80 µg/ml. The ethyl acetate fraction also had a considerable concentration of total phenolic compounds and flavonoids and exhibited significant (p < .05) inhibitory effects on acetylcholinesterase with an IC50 of 30 ± 0.30 µg/ml. Therefore, the aerial parts of S. tetragona contained high levels of biologically active compounds, making it a potential source for developing new plant-based pharmaceuticals and nutraceuticals to enhance human health