title: Key Structural Features of Azanaphthoquinone Annelated Pyrrole Derivative as Anticancer Agents Based on the Rational Drug Design Approaches.
abstract: Azanaphthoquinone annelated pyrrole derivatives have been developed and synthesized with a continuous attempt to develop novel DNA intercalating agents as anti-cancer compounds with lower organ toxicity. With the remarkable antiproliferative activity of synthesized azanaphthoquinone annelated pyrrole derivatives, a structurally novel scaffold of these compounds is appropriated for further development of novel anti-cancer agents. Therefore, in the present study, 3D QSAR study (CoMSIA) was applied on 28 azanaphthoquinone annelated pyrrole derivatives to evaluate the structural requirement of these compounds. The resulting CoMSIA model is satisfied with r(2) of 0.99 and q(2) of 0.65. The interpretation of CoMSIA contours reveals the significant importance of steric, electrostatic, hydrophobic and hydrogen acceptor descriptors on the activities of azanaphthoquinone annelated pyrrole derivatives. Remarkably, the structural requirement of six substituent positions on the azanaphthoquinone annelated pyrrole scaffold was elucidated here. This result is the useful concept for design of new and more active azanaphthoquinone annelated pyrrole derivatives. Moreover, MD simulations using AMBER program were performed to model the binding of azanaphthoquinone annelated pyrrole derivatives in the intercalation site of the DNA duplex. Based on MD simulations, the information in terms of ligand-DNA interaction, complex structure and binding free energy was provided in this work. Therefore, the integrated results are informative for further modification of azanaphthoquinone annelated pyrrole scaffold leading to gain novel azanaphthoquinone annelated pyrrole derivatives possessing better antiproliferative activity.
authors.affiliation: Department of Chemistry, Ubon Ratchathani University, 85 Sathollmark Rd., Warinchamrap, Ubonratchathani, 34190, Thailand phone/fax:+66 45 353400 4124/+66 45 288379.
authors.forename: Pharit
authors.initials: P
authors.lastname: Kamsri
authors.affiliation: Division of Science, Faculty of Liberal Arts and Sciences, Nakhon Phanom University, Nakhon Phanom 48000, Thailand.
authors.forename: Auradee
authors.initials: A
authors.lastname: Punkvang
authors.affiliation: Department of Chemistry, Ubon Ratchathani University, 85 Sathollmark Rd., Warinchamrap, Ubonratchathani, 34190, Thailand phone/fax:+66 45 353400 4124/+66 45 288379.
authors.forename: Nipawan
authors.initials: N
authors.lastname: Pongprom
authors.affiliation: Department of Chemistry, Ubon Ratchathani University, 85 Sathollmark Rd., Warinchamrap, Ubonratchathani, 34190, Thailand phone/fax:+66 45 353400 4124/+66 45 288379.
authors.forename: Apinya
authors.initials: A
authors.lastname: Srisupan
authors.affiliation: Department of Chemistry, Kasetsart University, Chatuchak, Bangkok, 10900, Thailand.
authors.forename: Patchreenart
authors.initials: P
authors.lastname: Saparpakorn
authors.affiliation: Department of Chemistry, Kasetsart University, Chatuchak, Bangkok, 10900, Thailand.
authors.forename: Supa
authors.initials: S
authors.lastname: Hannongbua
authors.affiliation: Department of Pharmaceutical Technology and Biopharmaceutics, Faculty of Life Sciences, University of Vienna, Althanstrasse 14, Vienna, Austria.|Institute for Theoretical Chemistry, University of Vienna, Waehringerstrasse 17, Vienna, Austria.
authors.forename: Peter
authors.initials: P
authors.lastname: Wolschann
authors.affiliation: Department of Chemistry, Ubon Ratchathani University, 85 Sathollmark Rd., Warinchamrap, Ubonratchathani, 34190, Thailand phone/fax:+66 45 353400 4124/+66 45 288379. pornpan_ubu@yahoo.com.
authors.forename: Pornpan
authors.initials: P
authors.lastname: Pungpo
keywords: Anti-cancer; Azanaphthoquinone; Intercalating agent; MD simulations; QSAR