DZ-BAU2021-14N AS NOVEL PYRAZOLOPYRIDINE NANOCRYSTALS: APPRAISAL OF ANTICANCER ACTIVITY AGAINST HCT-116 AND HT-29 COLORECTAL CANCER CELL LINES

Authors

Zahra Kassem, Lab Technician in Research Pharmaceutical Technology Lab, Pharmaceutical Sciences Department, Faculty of Pharmacy, Beirut Arab University, Beirut, LebanonFollow
Soumaiah Abou Staiteieh, Genomic Surveillance and Biotherapy (GSBT) Laboratory, Biology Department, Faculty of Sciences, R. Hariri Campus, Lebanese University, Hadath, LebanonFollow
Jamal Nasr, Genomic Surveillance and Biotherapy (GSBT) Laboratory, Biology Department, Faculty of Sciences, R. Hariri Campus, Lebanese University, Hadath, LebanonFollow
Amina Mneimneh, Postgraduate Student, Faculty of Pharmacy, Beirut Arab University, Beirut, LebanonFollow
Ali Youssef, Research Associate, Faculty of Arts and Sciences, American University of Beirut, Beirut, LebanonFollow
Nadine Darwiche, Professor, Department of Biochemistry and Molecular Genetics, American University of Beirut, LebanonFollow
Doaa Issa, Associate Professor of Medicinal Chemistry, Pharmaceutical Sciences Department, Faculty of Health Pharmacy, Beirut Arab University, Beirut, LebanonFollow
Raghida Bou Merhi, Genomic Surveillance and Biotherapy (GSBT) Laboratory, Biology Department, Faculty of Sciences, Lebanese University, Hadath, LebanonFollow
Mohammed Mehanna, Assistant Professor, Faculty of Pharmacy, Beirut Arab University, Beirut, LebanonFollow

English Title

DZ-BAU2021-14N AS NOVEL PYRAZOLOPYRIDINE NANOCRYSTALS: APPRAISAL OF ANTICANCER ACTIVITY AGAINST HCT-116 AND HT-29 COLORECTAL CANCER CELL LINES

Keywords

Pyrazolopyridine, Nanocrystals, Colorectal cancer, Antiproliferative, HCT-116, HT-29, NCM-460D

Disciplines

Chemicals and Drugs | Heterocyclic Compounds | Medicine and Health Sciences | Pharmaceutical Preparations

Abstract

Mentioning DZ-BAU2021-14 (C₁₉H₁₇N₅O₂,347.370 g/mol) developed in BAU Labs, its promising preliminary antitumor effect nominated it to be selected as a lead antiproliferative compound against colorectal cancer cell lines owing to its proved Cyclin Dependent Kinase 2 (CDK2) inhibition (Kassem et al., 2021). Solving many problems restricting traditional cancer therapy, nanotechnology is offering safety margins and targeted delivery of poorly soluble drug. The potential effect of this compound was combined with the advantages of nanotechnology, precisely nanocrystals to achieve better antiproliferative and hopeful less cytotoxic patterns. The nanocrystals DZ-BAU2021-14N were prepared by an antisolvent precipitation technique using Poloxamer 407 and Cremophor^® RH 40 as stabilizers. The nanocrystals were obtained with a nanometric particle size (89.80 ± 11.2 nm) and a negative zeta potential (-32.6 ± 0.50 mV) and were stable at 4 ± 0.5°C with no significant change in particle size or zeta potential. The anticancer activity of DZ-BAU2021-14 and DZ-BAU2021-14N were assessed. Their antiproliferative effects against colorectal cancer cell lines HCT-116 and HT-29 were studied via viability assay. In addition, their cytotoxic effects on non-tumorigenic cell lines NCM-460D were evaluated and respective IC50 values were determined. Different responses were obtained; DZ-BAU2021-14N provided lower IC50 on HCT-116 compared to the free drug DZ-BAU2021-14 (27 and 22 µM, respectively). The safety profile of the free drug was reflected by its IC50 on NCM-460D of 200µM while that of drug nanocrystals showed relative cytotoxicity with IC50 of 33µM, and this requires further investigation to study this response.

Recommended Citation

Kassem, Zahra; Abou Staiteieh, Soumaiah; Nasr, Jamal; Mneimneh, Amina; Youssef, Ali; Darwiche, Nadine; Issa, Doaa; Bou Merhi, Raghida; and Mehanna, Mohammed (2021) "DZ-BAU2021-14N AS NOVEL PYRAZOLOPYRIDINE NANOCRYSTALS: APPRAISAL OF ANTICANCER ACTIVITY AGAINST HCT-116 AND HT-29 COLORECTAL CANCER CELL LINES," BAU Journal - Health and Wellbeing: Vol. 4: Iss. 1, Article 9.
DOI: https://doi.org/10.54729/2789-8288.1163