A Theoretical Study on Electronic Structure and Structure-Activity Properties of Novel Drug Precursor 6-Acylbenzothiazolon Derivatives

SIDIR Y. G., SIDIR İ., TAŞAL E., Ogretir C.

INTERNATIONAL JOURNAL OF QUANTUM CHEMISTRY, vol.111, no.14, pp.3616-3629, 2011 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Volume: 111 Issue: 14
  • Publication Date: 2011
  • Doi Number: 10.1002/qua.22736
  • Journal Name: INTERNATIONAL JOURNAL OF QUANTUM CHEMISTRY
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.3616-3629
  • Keywords: analgesic activity, acylbenzothiazolon, molecular descriptors, SAR, log P, octanol-water partition coefficient, AM1, DFT, QUANTITATIVE STRUCTURE-ACTIVITY, DENSITY-FUNCTIONAL THEORY, QSAR, HARDNESS, INDEX, ELECTRONEGATIVITY, MUTAGENICITY, REACTIVITY, PRINCIPLE, CHEMISTRY
  • Eskisehir Osmangazi University Affiliated: Yes

Abstract

In this work, electronic properties and structure-activity relationship (SAR) parameters of 20 novel drug precursor 6-acylbenzothiazolon derivatives with analgesic activity have been investigated theoretically by performing Austin Model-1 (AM1) and DFT-B3LYP/6-31G (d) calculations with the aim to correlate the properties of each substance-particularly electronic properties and SAR parameters-with the biological interactions that are linked to their pharmacological effects. Their molecular properties were related to the biological activity of these drug precursor molecules. The relationship between octanol-water partition coefficient (log P) and each of the SAR parameters [ELUMO-HOMO, molecular volume (V-m), ionization potential (IP), electron affinity, electronegativity (chi), chemical hardness (eta), chemical softness (S), electrophilic index (omega), and molar refractivity] present linear correlation except for IP and chi. This result suggests that there are future prospects for designing or developing new drugs based on the correlation between the theoretically calculated parameters. According to AM1 calculation, the values of heat of formation of 6-acylbenzothiazolon derivatives are negative (exothermic), which shows that these molecules are thermodynamically stable. ELUMO-HOMO energy levels of the studied molecules are 4-5 eV, which also indicate that they are kinetically unstable. (C) 2010 Wiley Periodicals, Inc. Int J Quantum Chem 111: 3616-3629, 2011