Synthesis of new bis(dimethylamino)benzophenone hydrazone for diabetic management: In-vitro and in-silico approach
Momin Khan,
Ghulam Ahad,
Aftab Alam,
Saeed Ullah,
Ajmal Khan,
Kanwal,
Uzma Salar,
Abdul Wadood,
Amar Ajmal,
Khalid Mohammed Khan,
Shahnaz Perveen,
Jalal Uddin,
Ahmed Al-Harrasi
Affiliations
Momin Khan
Department of Chemistry, Abdul Wali Khan University, Mardan, 23200, Pakistan; Corresponding author.
Ghulam Ahad
Department of Chemistry, Abdul Wali Khan University, Mardan, 23200, Pakistan
Aftab Alam
Department of Chemistry, University of Malakand, Chakdara, Lower Dir, 18800, Pakistan
Saeed Ullah
Natural & Medical Sciences Research Center, University of Nizwa, P.O Box 33, Postal Code 616, Birkat Al Mauz, Nizwa, Oman
Ajmal Khan
Natural & Medical Sciences Research Center, University of Nizwa, P.O Box 33, Postal Code 616, Birkat Al Mauz, Nizwa, Oman; Corresponding author.
Kanwal
H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, 75270, Pakistan
Uzma Salar
H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, 75270, Pakistan
Abdul Wadood
Department of Biochemistry, Abdul Wali Khan University, Mardan, 23200, Pakistan
Amar Ajmal
Department of Biochemistry, Abdul Wali Khan University, Mardan, 23200, Pakistan
Khalid Mohammed Khan
H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, 75270, Pakistan; Department of Clinical Pharmacy, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, P.O. Box 31441, Dammam, Saudi Arabia
Inhibiting α-glucosidase is a reliable method for reducing blood sugar levels in diabetic individuals. Bis(dimethylamino)benzophenone derivatives 1–27 were synthesized from bis(dimethylamino)benzophenone via two-step reaction. Different spectroscopic techniques, including EI-MS and 1H NMR, were employed to characterize all synthetic derivatives. The elemental composition of synthetic compounds was confirmed by elemental analysis and results were found in agreement with the calculated values. The synthetic compounds 1–27 were evaluated for α-glucosidase inhibitory activity, except five compounds all derivatives showed good to moderate inhibitory potential in the range of IC50 = 0.28 ± 2.65 - 0.94 ± 2.20 μM. Among them, the most active compounds were 5, 8, 9, and 12 with IC50 values of 0.29 ± 4.63, 0.29 ± 0.93, 0.28 ± 3.65, and 0.28 ± 2.65, respectively. Furthermore, all these compounds were found to be non-toxic on human fibroblast cell lines (BJ cell lines). Kinetics study of compounds 8 and 9 revealed competitive type of inhibition with Ki values 2.79 ± 0.011 and 3.64 ± 0.012 μM, respectively. The binding interactions of synthetic compounds were also confirmed through molecular docking studies that indicated that compounds fit well in the active site of enzyme. Furthermore, a total of 30ns MD simulation was carried out for the most potent complexes of the series. The molecular dynamics study revealed that compound-8 and compound-12 were stable during the MD simulation.
