Publications by authors named "Rabab Albashiti"

5 Publications

  • Page 1 of 1

Antiproliferative properties of 7,8-Ethylene Diamine Chelator-Lipophilic Fluoroquinolone Derivatives Against colorectal cancer Cell Lines.

Anticancer Agents Med Chem 2021 Jun 23. Epub 2021 Jun 23.

School of Pharmacy, University of Jordan, Queen Rania Street, Amman 11942, Jordan.

Background: Cancer is one of the most overwhelming diseases nowadays. It is considered the second cause of death after cardiovascular diseases. Due to the diversity of its types, stages, and genetic origin, there is no available drug to treat all cancers. Serious side effects and resistance to existing drugs are other problems in this struggle against cancer. In such quest, fluoroquinolones (FQs) offer a future promise as antiproliferative compounds due to safety, low cost, and lack of resistance.

Objectives: Therefore, this work aims at developing lipophilic FQs and screening their antiproliferative activity against colorectal cancer.

Methods: Nine prepared FQs were investigated for antiproliferative activity utilizing in vitro SRB method. In comparison to the antiproliferative agent cisplatin, the assessment of antiproliferative activities of these novel FQs in a panel of colorectal cancer cell (crc) lines (HT29, HCT116, SW620, CACO2, SW480) and normal periodontal ligament fibroblasts for safety examination was performed. Antibacterial activity (MIC) was conducted against Staphylococcus aureus and Escherichia coli standard strains using the broth double dilution method. Antioxidant properties were suspected as the mechanism of antiproliferative activity; thus, a DPPH test was performed to analyze the radical scavenging potency of FQs compared to ascorbic acid as a reference agent. FQs compounds 3-5(a-c) were prepared, characterized and their structure was confirmed using spectroscopy techniques.

Results: All compounds manifested good to excellent antiproliferative activity on HT29, HCT116, and SW620 with high safety index. The reduced series 4a, 4b, and 4c exerted excellent micro to nanomolar antiproliferative activities on HT29, HCT116, and SW620, which were stronger than the reference cisplatin against all cells. The reduced group of compounds 4(a-c) revealed higher potency vs. both nitro and triazolo groups. On cell lines HT29, HCT116, and SW620 reduced 4a with 7,8-ethylene diamine substitution revealed the highest antiproliferative efficacy (IC50 value) approaching nanomolar affinity with higher safety vs. cisplatin. The most active compound, 4a, exhibited significant potency against HCT116 and SW620 with IC50 0.6 and 0.16 µM, respectively. Novel FQs (4a, 4b, and 4c) also showed strong radical scavenging activity with IC50 values (µM) 0.06, 23, and 7.99, respectively. Exquisitely 4a revealed a similar pattern of activity to doxorubicin, indicating a similar mechanism of action. Strong antiproliferative and weak antibacterial activities of series 4 endorse that their mechanism involves eukaryotic topoisomerase II inhibition. This work has revealed novel FQs with excellent anticancer activity against 5 colorectal cancer (HT29, HCT116, SW620, CACO2, SW480) cell lines with a potential chelation mechanism due to 7,8-ethylene diamine chelator bridge.

Conclusions: The new FQs have confirmed that more lipophilic compounds could be more active as hypothesized. The p-halogenated aniline, N1-Butyl group in addition to 3-COOH, 8-NH2 are all essential requirements for strong antiproliferative FQ of our FQ scaffold. This work emphasizes the role of C-8 amino as part of ethylene diamine group as an essential requirement for antiproliferative FQs for the first time in the literature, entailing its role toward potential antneoplastic FQs.
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http://dx.doi.org/10.2174/1871520621666210623111744DOI Listing
June 2021

Pharmacological Evaluation of Novel Isonicotinic Carboxamide Derivatives as Potential Anti-Hyperlipidemic and Antioxidant Agents.

Arch Pharm (Weinheim) 2017 Oct 24;350(10). Epub 2017 Aug 24.

Faculty of Pharmacy, University of Jordan, Amman, Jordan.

Hyperlipidemia and oxidative stress have been implicated as contributing factors to the development of atherosclerosis and cardiovascular diseases (CVDs). Currently, a large number of antihyperlipidemic medications are conveniently available in the market. Nonetheless, the majority of antihyperlipidemics lack the desired safety and efficacy. Thus, the present study was undertaken to evaluate the potential effect of novel N-(benzoylphenyl)pyridine-4-carboxamide and N-(9,10-dioxo-9,10-dihydroanthracenyl)pyridine-4-carboxamide derivatives in controlling hyperlipidemia and oxidative stress using the Triton WR-1339-induced hyperlipidemic rat model for antihyperlipidemic activity and the DPPH radical scavenging assay for antioxidant activity. This study revealed the antihyperlipidemic activities of some of the newly synthesized, novel carboxamide derivatives, mainly C4 and C12 (p < 0.05). The majority of the compounds displayed a relatively low or no DPPH radical scavenging effect, with C20 possessing the best radical scavenging effect (22%) among all. This research opens the door for new potential antihyperlipidemic compounds derived from isonicotinic acid. N-(3-Benzoylphenyl)pyridine-4-carboxamide (C4) was found to have promising lipid-lowering and antioxidant effects, which may create a protective effect against CVDs, by reducing the LDL-C levels and diminishing the generation of reactive oxygen species.
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http://dx.doi.org/10.1002/ardp.201700024DOI Listing
October 2017

Antilipase and antiproliferative activities of novel fluoroquinolones and triazolofluoroquinolones.

Chem Biol Drug Des 2017 Dec 1;90(6):1282-1294. Epub 2017 Aug 1.

Faculty of Pharmacy, Al-Zaytoonah University of Jordan, Amman, Jordan.

Fluoroquinolones (FQs) have been identified recently as potent inhibitors of pancreatic lipase (PL). The aim of this study was to synthesize novel FQs and triazolofluoroquinolones (TFQs) and to evaluate them in vitro with respect to their antilipolytic efficacy and potency properties. The PL-IC values of 12 FQs and TFQs (3 (a-c)-6 (a-c)) were in the range of 12.5-189.1 μm. These values are further supported by docking studies. The suggested association between obesity and colorectal cancer initiated the evaluation of antiproliferative activity of the new FQs and TFQs against a panel of obesity-related colorectal cells (HT29, HCT116, SW620 CACO2, and SW480). Sulforodamine B colorimetric assay revealed that some derivatives exhibited unselective cytotoxicity against HT29, HCT116, SW620 CACO2, and SW480. Remarkably, FQ 4a's selective cytotoxicity against HCT116 was found valuable with IC value of 4.2 μm which exceeds that of cisplatin with a substantial selective cytotoxicity in periodontal ligament fibroblasts. In conclusion, FQ and TFQ derivatives may unveil new antiobesity and anticancer agents in the future.
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http://dx.doi.org/10.1111/cbdd.13049DOI Listing
December 2017

Lipid lowering activity of novel N-(benzoylphenyl)pyridine-3-carboxamide derivatives in Triton WR-1339-induced hyperlipidemic rats.

J Enzyme Inhib Med Chem 2016 25;31(sup4):138-144. Epub 2016 Aug 25.

a Faculty of Pharmacy , The University of Jordan , Amman , Jordan and.

Context: Dyslipidemia is a major risk factor for the development of cardiovascular diseases. Many dyslipidemic patients do not achieve their target lipid levels with the currently available medications, and most of them may experience many side effects.

Objective: The present work aimed toward identifying a new class of novel nicotinic acid-carboxamide derivatives as promising antihyperlipidemic compounds.

Materials And Methods: Six novel N-(benzoylphenyl)pyridine-3-carboxamide derivatives were synthesized using acid chloride pathways. All structures were confirmed using H-NMR, C-NMR, IR, and HRMS. The evaluation of biological activity was conducted using Triton WR-1339-induced hyperlipidemic rats model.

Results: This study revealed that some of the newly synthesized novel N-(benzoylphenyl)pyridine-3-carboxamide derivatives mainly C4 and C6 possessed significant antihyperlipidemic activities on lipid components TG and TC (p value <0.05).

Discussion And Conclusion: This research opens the door for new potential antihyperlipidemic compounds derived from nicotinic acid that need further optimization of their biological activities.
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http://dx.doi.org/10.1080/14756366.2016.1222581DOI Listing
February 2017

Design synthesis and antibacterial activity studies of new thiadiazoloquinolone compounds.

J Enzyme Inhib Med Chem 2014 Dec 10;29(6):777-85. Epub 2014 Feb 10.

Chemistry Department, Faculty of Science, The University of Jordan , Amman , Jordan .

Abstract New 9-(alkyl/aryl)-4-fluoro-6-oxo[1,2,5]thiadiazolo[3,4-h]quinoline-5-carboxylic acids and their esters were designed and synthesized. A detailed discussion of the reactions utilized in the preparation of the intermediate and target compounds is reported. All the newly synthesized compounds were fully characterized using all the physico-chemical means needed. All the intermediates and the final esters and acids were tested against bacterial and fungal strains. The acids 25a and 25c proved to be very active against Gram positive and Gram negative bacteria with MIC 0.15-3 µg/mL. The structure-activity relationship of antibacterial thiadiazoloquinolones shows that compounds 25a and 25c are twice less potent than the corresponding cyclopropyl derivative 16. Therefore, the cyclopropyl moiety on N-9 seems to be the most suitable substituent.
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http://dx.doi.org/10.3109/14756366.2013.855925DOI Listing
December 2014
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