| Autor: |
Samaha D; Pharmaceutical Chemistry Department, Faculty of Pharmacy, Helwan University, Helwan, Egypt.; Institute of Chemistry, Humboldt-Universität zu Berlin, Berlin, Germany., Mahmoud S; Pharmaceutical Chemistry Department, Faculty of Pharmacy, Helwan University, Helwan, Egypt., Mohamed MS; Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Helwan University, Helwan, Egypt., Abdullah RS; Environment Division, National Institute of Oceanography and Fisheries (NIOF), Alexandria, Egypt.; Department of Pharmaceutical Sciences, Irma Lerma Rangel School of Pharmacy, Texas A&M University, College Station, TX, USA., A Abou Taleb N; Pharmaceutical Chemistry Department, Faculty of Pharmacy, Helwan University, Helwan, Egypt., Nagamatsu T; Laboratory of Curative Creation Study for Geriatric-diseases Prevention, Faculty of Pharmacological Sciences, Sojo University, Kumamoto, Japan., Ali HI; Department of Pharmaceutical Sciences, Irma Lerma Rangel School of Pharmacy, Texas A&M University, College Station, TX, USA. |
| Abstrakt: |
This study describes the development of novel alloxazine analogues as potent antitumor agents with enhanced selectivity for tumour cells. Twenty-nine out of 45 newly compounds were investigated in vitro for their growth inhibitory activities, against two human tumour cell lines, namely, the human T-cell acute lymphoblastoid leukaemia cell line (CCRF-HSB-2) and human oral epidermoid carcinoma cell line (KB), and the antitumor agent "Ara-C" was used as a positive reference in this investigation. Compounds 9e and 10J were the highest among their analogues, against both tumour cell lines (CCRF-HSB-2 and KB). Correlation analyses demonstrated a strong relationship between the IC 50 values and AutoDock binding free energy or calculated inhibition ( K i ). The study delves into structure-activity relationships (SARs) through advanced modelling tools integrated with structure-based drug design (SBDD) using GOLD 5.2.2, AutoDock 4.2, and Accelrys Discovery Studio 3.5. Physicochemical properties, pharmacokinetics, drug-likeness, and toxicity predictions of the most potent alloxazine derivatives were conducted using ProTox-II and Swiss ADME for effective antitumor agents with improved selectivity. |
