Computational Chemical Property Prediction and Anticancer Simulation of Heterocyclic Molecules

Title

Computational Chemical Property Prediction and Anticancer Simulation of Heterocyclic Molecules

Creator

Parakkal, Sheryl Cherian

Contributor

Datta, Riya

Description

The Density Functional Theory (DFT) technique is popularly employed in establishing organic molecules' structural properties and reactivities. The B3LYP hybrid functional with the basis set 6-311G++(d,p) is utilised in the computational calculations with Gaussian 09W software. The DFT studies include energy minimisation (geometry optimisation), frontier molecular orbitals (FMO) analyses, theoretical UV spectral computation, natural bond orbital (NBO) evaluation, Topological analyses using Multiwfn 3.8 software are performed to evaluate the Pauli repulsion in atomic orbitals (as shown by ELF (Electron Localisation Function) maps), the areas of strong and weak pi-delocalisation in the molecules (as depicted in LOL (Localised Orbital Locator) maps) and the weak non-covalent intra-molecular interactions (as indicated in colour maps of RDG (Reduced Density Gradient)). Pharmacological evaluation is performed using SwissADME, ADMETLab 2.0, and PreADMET online tools. Molecular docking is performed using AutoDock Tools 1.5.6 with select anticancer target proteins to predict the bioactivity potential of the title molecules. The molecules studied in the work include a spiro compoun d, spiro[1H-indole-3,2-3H-1,3- benzothiazole]-2-one, a 2(3H)-furanone, 3,3,5-triphenylfuran-2(3H)-one, and a benzo[d]imidazole, 5,6-dichloro-1-cyclopentyl-2-(methylsulfinyl)-1H- benzimidazole. In addition, comparative studies are performed on the structure and reactivity of spirobrassinin derivatives, spirocyclic isatin-derivative analogues, and 3(2H)-furanones, and these three classes of molecules have already been predicted to possess anticancer properties in vitro. Interesting properties emerge in the preliminary theoretical investigations for these molecules, particularly in the FMO, the NLO and the molecular docking studies. The theoretical studies explore the reactivity, structure, and stability of the molecules under study, and biological evaluation examines their potential as lead compounds for cancer therapeutics. These studies can be further extended to include experimental validation and in vitro and in vivo tests to confirm further the efficacy of the anticancer action as well as the potential toxicity of the compounds. The theoretical investigations provide a database of information that could be useful for experimental scientists and medicinal chemists who primarily focus on drug design and discovery in their research so that they can narrow down the number of possible lead compounds from the vast chemical space of organic compounds that possess drug-like characteristics.

Source

Author's Submission

Date

2024-01-01

Publisher

Christ(Deemed to be University)

Subject

Chemistry

Rights

Open Access

Relation

61000341

Format

PDF

Language

English

Type

PhD

Identifier

http://hdl.handle.net/10603/575077