Preliminary SAR analysis of novel antiproliferative N6,5′-bis-ureidoadenosine derivatives

Synthesis and Evaluation as Antitumor Agents of 1,4‐Naphthohydroquinone Derivatives Conjugated with Amino Acids and Purines

“…Furthermore, compounds 4a – 8a are more cytotoxic than several conjugates reported in the literature such as platinum complexes of enantiomerically pure α‐trifluoromethyl alanine , 1,4‐bis(2‐aminoethylamino)anthraquinone–, ametantrone–, and mitoxantrone–amino acid conjugates and more than naphthalimide–leucine conjugates against A‐549 and/or MCF‐7 cells. In the group of purine–naphthohydroquinone conjugates 10 – 13 , the fully aromatized compounds 10a – 13a (GI 50 2.9–8.7 μM) also showed higher cytotoxicity than the corresponding 5,8‐dihydro‐ ( 10b – 13b ) or 5,6,7,8‐tetrahydro‐ ( 10c – 13c ) derivatives against A‐549 or HT‐29 cultured cells. Their GI 50 values were in the same range or better than those observed for hybrid naphthohydroquinone–nucleic base mimics previously reported by us , also than 6,5′‐bis‐ureidoadenosine derivatives , purine derivatives of allofuranose , benzoxazepin‐purine derivatives , and bis‐ N 9 ‐(methyl‐phenylmethyl)purine derivatives . Furthermore, among those evaluated compounds, one of the most active against the three cell lines assayed is the guanine–naphthohydroquinone hybrid 13a , with a GI 50 value of 3.0–3.1 μM, showing for the MCF‐7 cell line the same cytotoxicity as observed with the standard drug doxorubicin.…”

Solvent-driven structural topology involving energetically significant intra- and intermolecular chelate ring contacts and anticancer activities of Cu(ii) phenanthroline complexes involving benzoates: experimental and theoretical studies

“…The analysis of SAR enables to understand specic chemical group(s) in molecular structure related to possible biological activities in the organism. 87 From the docking based SAR analysis it has been observed that oxygen atoms with atom label -1 and 3 and nitrogen with 1 and 2 in complex 1 while, in complex 2 oxygen atoms with atom label -1, 2, 3, 4 and 5 showed major role during interactions with B-RAF kinase, CC chemokine receptor, EGFR kinase domain and PI3K-gamma receptors. SAR analysis on the basis of available bioassays in NCBI database, it was found that phenanthroline nuclei inhibit MTORC1, PR, ER-beta and AR signaling pathways.…”

Synthesis and Cytostatic Effect of 3’-deoxy-3’-C-Sulfanylmethyl Nucleoside Derivatives with d-xylo Configuration

“…For example, Herczegh and colleagues have demonstrated that the TBDMS-protected leinamycin-nucleosides showed higher growth inhibitory activity toward human cancer cells than the corresponding deprotected derivatives [41]. Bis-ureidoadenosine derivatives, reported by Peterson's group, were found to display a higher antiproliferative activity in the protected form, and the silylated compounds showed the highest activity [42,43]. Moreover, in the case of the ribothymidine-derived reverse transcriptase inhibitor TSAO-T, the tert-butyldimethylsilyl group at 5' positions is found to play a crucial role in the biological activity [44].…”