DFT/B3LYP calculations, in vitro cytotoxicity and antioxidant activities of steroidal pyrimidines and their interaction with HSA using molecular docking and multispectroscopic techniques

• Published in: Bioorganic chemistry Vol. 73; pp. 83 - 99
• Main Authors: Ali, Abad, Asif, Mohd, Alam, Parvez, Jane Alam, Mohammad, Asif Sherwani, Mohd, Hasan Khan, Rizwan, Ahmad, Shabbir, Shamsuzzaman
• Format: Journal Article
• Language: English
• Published: SAN DIEGO Elsevier Inc 01.08.2017; Elsevier
• Subjects: Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Antioxidant; Antioxidants - chemical synthesis; Antioxidants - chemistry; Antioxidants - pharmacology; Apoptosis - drug effects; Biochemistry & Molecular Biology; Cell Line, Tumor; Cell Proliferation - drug effects; Chemistry; Chemistry, Organic; Cytotoxicity; DFT; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; HSA; Humans; Life Sciences & Biomedicine; Molecular Docking Simulation; Molecular Structure; Physical Sciences; Pyrimidine; Pyrimidines - chemical synthesis; Pyrimidines - chemistry; Pyrimidines - pharmacology; Quantum Theory; Science & Technology; Steroids - chemical synthesis; Steroids - chemistry; Steroids - pharmacology; Structure-Activity Relationship; Cytotoxicity; DFT; Antioxidant; HSA; Pyrimidine; CHOLESTEROL; HUMAN SERUM-ALBUMIN; FT-RAMAN; INSIGHT; FREE-RADICALS; SPECTROSCOPIC INVESTIGATIONS; ANTICANCER; DNA; BINDING; DERIVATIVES
• ISSN: 0045-2068; 1090-2120
• DOI: 10.1016/j.bioorg.2017.06.001

[Display omitted] •A synthesis of novel steroidal pyrimidines has been performed.•The interaction of compounds with HSA was also carried out with multispectroscopic techniques and docking studies.•MTT assay was carried out to check the toxicity of new compounds.•Antioxidant activity of the synthesized compounds by various methods have also been investigated. As a part of our continuing program on the synthesis of steroidal heterocycles, it has been prepared a series of novel steroidal pyrimidine derivatives 4–6via TMSCl, steroidal ketones (1c–3c), urea and benzaldehyde. The systems presented here, are novel scaffolds and have not been described before at 6th position of steroidal-6-one (1c–3c). Structural assignment of newly synthesized compounds was performed by DFT/B3LYP calculations as well as spectral and analytical data. The interactions of compounds (4–6) with HSA were studied by fluorescence spectroscopy, DLS, CD and molecular docking, under imitated physiological conditions. The antitumor activity has been tested in vitro against three cancer cell lines MDA-MB231 (breast carcinoma), HeLa (human cervical carcinoma), HepG2 (hepatic carcinoma) and one non-cancer normal cell lines, PBMCs (peripheral blood mononuclear cell) by MTT assay. In addition, in vitro antioxidant activity and apoptosis assay of the synthesized compounds (4–6) have also been investigated.