School of Basic Sciences, Indian Institute of Technology Bhubaneswar, Bhubaneswar, India.
School of Applied Sciences, KIIT Deemed to Be University, Bhubaneswar, 751024, Odisha, India.
Arch Biochem Biophys. 2019 Apr 15;665:107-113. doi: 10.1016/j.abb.2019.03.001. Epub 2019 Mar 6.
Dapsone is a sulfone drug mainly used as anti-microbial and anti-inflammatory agent for the treatment of various diseases including leprosy. Recently, its interaction with protein (bovine serum albumin) is evidenced. But, the binding propensity of this anti-mycobacterial drug towards DNA is still unknown. Also, the mode of dapsone-DNA interaction (if any) is still an unknown quantity. In this study, we have taken a thorough attempt to understand these two unknown aspects using various biophysical and in silico molecular docking techniques. Both UV-visible and fluorescence titrimetric studies indicated that dapsone binds to CT-DNA with a binding constant in order of 10 M. Circular dichroism, thermal denaturation and viscosity experiments revealed that dapsone binds to the grooves of CT-DNA. Competitive DNA binding studies clearly indicated the minor groove binding property of this anti-mycobacterial drug. Molecular docking provided detailed information about the formation of hydrogen bonding in the dapsone-DNA complex. This in silico study further revealed that dapsone binds to the AT-rich region of the minor groove of DNA having a relative binding energy of -6.22 kcal mol. Overall, all these findings evolved from this study can be used for better understanding the medicinal importance of dapsone.
氨苯砜是一种砜类药物，主要用作抗菌和抗炎剂，用于治疗包括麻风病在内的各种疾病。最近，已经证实其与蛋白质（牛血清白蛋白）相互作用。但是，这种抗分枝杆菌药物与 DNA 的结合倾向仍然未知。此外，氨苯砜-DNA 相互作用（如果有的话）的模式仍然是一个未知数。在这项研究中，我们使用各种生物物理和计算机对接分子 docking 技术，对这两个未知方面进行了深入的尝试。紫外可见和荧光滴定研究表明，氨苯砜与 CT-DNA 的结合常数约为 10 M。圆二色性、热变性和粘度实验表明，氨苯砜与 CT-DNA 的沟结合。竞争性 DNA 结合研究清楚地表明，这种抗分枝杆菌药物具有小沟结合特性。分子对接提供了关于氨苯砜-DNA 复合物中氢键形成的详细信息。这项计算机研究进一步表明，氨苯砜与 DNA 小沟的富含 AT 区域结合，相对结合能为-6.22 kcal/mol。总的来说，这项研究得出的所有这些发现都可以用于更好地理解氨苯砜的药用重要性。
