Department of Chemistry, National Institute of Technology, Hamirpur, Himachal Pradesh, India.
Adv Exp Med Biol. 2011;696:385-400. doi: 10.1007/978-1-4419-7046-6_39.
Numbers of drugs are being synthesized every year to meet the target of safe and disease-free society. Presently molecular modeling technique is used to unfold the mechanism of action of drugs alone or in conjunction with experimental methodologies. There are a number of drugs which are successfully developed using this methodology. Mitoxantrone (MTX) - 1, 4-dihydroxy-5, 8-bis {[2-(2-hydroxyethyl) amino] amino}-9, 10-anthracenedione is marketed under the name Novantrone, an anticancer drug used in chemotherapy. Its important analog ametantrone and various other analogs differ from one another in the position of side chain or functionalities on the chromophore eventually exhibit varied biological activities. DNA binding is an important phenomenon for anticancer activity of these drugs. In order to understand the interactions of the drug molecules with its receptor site, at atomic level, we have carried out computer simulations of drug and DNA alone and also in complex mode in water as a medium. All the simulations are being carried out using molecular operating environment (MOE) and X3DNA software tools on SUN SOLARIS platform. Interaction energy of all the drug molecules with DNA is determined and compared. Also the structural changes in DNA and drug before and after complex formation are studied extensively.
每年都有大量的药物被合成，以达到安全和无病社会的目标。目前，分子建模技术被用于单独或结合实验方法来揭示药物的作用机制。有许多药物是通过这种方法成功开发的。米托蒽醌（MTX）-1,4-二羟基-5,8-双{[2-（2-羟乙基）氨基]氨基}-9,10-蒽二酮以诺凡汀（Novantrone）的名称上市，这是一种用于化疗的抗癌药物。其重要的类似物氨甲蒽醌和其他各种类似物在侧链的位置或发色团上的官能团彼此不同，最终表现出不同的生物活性。DNA 结合是这些药物抗癌活性的一个重要现象。为了在原子水平上了解药物分子与其受体部位的相互作用，我们已经在水中作为介质，对药物和 DNA 单独以及复合物模式进行了计算机模拟。所有的模拟都是在 SUN SOLARIS 平台上使用分子操作环境（MOE）和 X3DNA 软件工具进行的。确定并比较了所有药物分子与 DNA 的相互作用能。还广泛研究了 DNA 和药物在形成复合物前后的结构变化。
