Synthesis of Novel Triazinoindole-Based Thiourea Hybrid: A Study on α-Glucosidase Inhibitors and Their Molecular Docking

Muhammad Taha; Foziah J Alshamrani; Fazal Rahim; Shawkat Hayat; Hayat Ullah; Khalid Zaman; Syahrul Imran; Khalid Mohammed Khan; Farzana Naz

doi:10.3390/molecules24213819

Synthesis of Novel Triazinoindole-Based Thiourea Hybrid: A Study on α-Glucosidase Inhibitors and Their Molecular Docking

Molecules. 2019 Oct 23;24(21):3819. doi: 10.3390/molecules24213819.

Authors

Muhammad Taha¹, Foziah J Alshamrani^{2

3}, Fazal Rahim⁴, Shawkat Hayat⁵, Hayat Ullah⁶, Khalid Zaman⁷, Syahrul Imran^{8

9}, Khalid Mohammed Khan¹⁰, Farzana Naz¹¹

Affiliations

¹ Department of Clinical Pharmacy, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, P.O. Box 1982, Dammam 31441, Saudi Arabia. mtaha@iau.edu.sa.
² Neurology Department, King Fahad hospital of University, Imam Abdulrahman Bin Faisal University, P.O. Box 1982, Dammam 34211, Saudi Arabia. Fshamrani@uod.edu.sa.
³ Department of Neuroscience Research, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, P.O. Box 1982, Dammam 31441, Saudi Arabia. Fshamrani@uod.edu.sa.
⁴ Department of Chemistry, Hazara University, Mansehra-21300, Khyber Pakhtunkhwa, Pakistan. fazalstar@gmail.com.
⁵ Department of Chemistry, Hazara University, Mansehra-21300, Khyber Pakhtunkhwa, Pakistan. shawkathayat866@yahoo.com.
⁶ Department of Chemistry, Hazara University, Mansehra-21300, Khyber Pakhtunkhwa, Pakistan. ayaanwazir366@gmail.com.
⁷ Department of Chemistry, Hazara University, Mansehra-21300, Khyber Pakhtunkhwa, Pakistan. khalidchemist69@yahoo.com.
⁸ Atta-ur-Rahman Institute for Natural Products Discovery (AuRIns), Universiti Teknologi MARA Puncak Alam Campus, 42300 Bandar Puncak Alam, Selangor D.E., Malaysia. imran@isiswa.uitm.edu.my.
⁹ Faculty of Applied Sciences, Universiti Teknologi MARA, Shah Alam 40450, Selangor D.E., Malaysia. imran@isiswa.uitm.edu.my.
¹⁰ H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan. khalid.khan@iccs.edu.
¹¹ Department of Chemistry, Jinnah University for Women, 5-C, Nazimabad, Karachi-74600, Pakistan. farzanahej@yahoo.com.

Abstract

A new class of triazinoindole-bearing thiosemicarbazides (1-25) was synthesized and evaluated for α-glucosidase inhibitory potential. All synthesized analogs exhibited excellent inhibitory potential, with IC₅₀ values ranging from 1.30 ± 0.01 to 35.80 ± 0.80 µM when compared to standard acarbose (an IC₅₀ value of 38.60 ± 0.20 µM). Among the series, analogs 1 and 23 were found to be the most potent, with IC₅₀ values of 1.30 ± 0.05 and 1.30 ± 0.01 µM, respectively. The structure-activity relationship (SAR) was mainly based upon bringing about different substituents on the phenyl rings. To confirm the binding interactions, a molecular docking study was performed.

Keywords: SAR; alpha-glucosidase; molecular docking study; synthesis; thiosemicarbazide; triazinoindole.

MeSH terms

Glycoside Hydrolase Inhibitors / chemical synthesis*
Glycoside Hydrolase Inhibitors / chemistry*
Molecular Docking Simulation*
Structure-Activity Relationship
Thiourea* / analogs & derivatives
Thiourea* / chemical synthesis
Thiourea* / chemistry
alpha-Glucosidases / chemistry*

Substances

Glycoside Hydrolase Inhibitors
alpha-Glucosidases
Thiourea

Abstract

MeSH terms

Substances

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