Synthesis, DFT Studies, Molecular Docking and Biological Activity Evaluation of Thiazole-Sulfonamide Derivatives as Potent Alzheimer’s Inhibitors
Shoaib Khan,
Hayat Ullah,
Muhammad Taha,
Fazal Rahim,
Maliha Sarfraz,
Rashid Iqbal,
Naveed Iqbal,
Rafaqat Hussain,
Syed Adnan Ali Shah,
Khurshid Ayub,
Marzough Aziz Albalawi,
Mahmoud A. Abdelaziz,
Fatema Suliman Alatawi,
Khalid Mohammed Khan
Affiliations
Shoaib Khan
Department of Chemistry, Hazara University, Mansehra 21120, Pakistan
Hayat Ullah
Department of Chemistry, University of Okara, Okara 56130, Pakistan
Muhammad Taha
Department of Clinical Pharmacy, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, P.O. Box 1982, Dammam 31441, Saudi Arabia
Fazal Rahim
Department of Chemistry, Hazara University, Mansehra 21120, Pakistan
Maliha Sarfraz
Department of Zoology, Wildlife and Fisheries, University of Agriculture Faisalabad, Sub-Campus, Toba Tek Singh 36050, Pakistan
Rashid Iqbal
Department of Agronomy, Faculty of Agriculture and Environment, The Islamia University of Bahawalpur, Bahawalpur 63100, Pakistan
Naveed Iqbal
Department of Chemistry, University of Poonch, Rawalakot 12350, Pakistan
Rafaqat Hussain
Department of Chemistry, Hazara University, Mansehra 21120, Pakistan
Syed Adnan Ali Shah
Faculty of Pharmacy, Universiti Teknologi MARA Cawangan Selangor Kampus Puncak Alam, Puncak Alam 42300, Selangor, Malaysia
Khurshid Ayub
Department of Chemistry, COMSATS University, Abbottabad Campus, Abbottabad 22060, Pakistan
Marzough Aziz Albalawi
Department of Chemistry, Alwajh College, University of Tabuk, Tabuk 71491, Saudi Arabia
Mahmoud A. Abdelaziz
Department of Chemistry, Faculty of Science, University of Tabuk, Tabuk 71491, Saudi Arabia
Fatema Suliman Alatawi
Department of Biochemistry, Faculty of Science, University of Tabuk, Tabuk 71491, Saudi Arabia
Khalid Mohammed Khan
H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan
Alzheimer’s disease is a major public brain condition that has resulted in many deaths, as revealed by the World Health Organization (WHO). Conventional Alzheimer’s treatments such as chemotherapy, surgery, and radiotherapy are not very effective and are usually associated with several adverse effects. Therefore, it is necessary to find a new therapeutic approach that completely treats Alzheimer’s disease without many side effects. In this research project, we report the synthesis and biological activities of some new thiazole-bearing sulfonamide analogs (1–21) as potent anti-Alzheimer’s agents. Suitable characterization techniques were employed, and the density functional theory (DFT) computational approach, as well as in-silico molecular modeling, has been employed to assess the electronic properties and anti-Alzheimer’s potency of the analogs. All analogs exhibited a varied degree of inhibitory potential, but analog 1 was found to have excellent potency (IC50 = 0.10 ± 0.05 µM for AChE) and (IC50 = 0.20 ± 0.050 µM for BuChE) as compared to the reference drug donepezil (IC50 = 2.16 ± 0.12 µM and 4.5 ± 0.11 µM). The structure-activity relationship was established, and it mainly depends upon the nature, position, number, and electron-donating/-withdrawing effects of the substituent/s on the phenyl rings.
