One pot synthesis of 5-hydroxyalkylated thiadiazine thiones: Implication in pain management and bactericidal properties
Asma Gul,
Sobia Ahsan Halim,
Ajmal Khan,
Rasool Khan,
P.A.N. Xian-Dao,
Salman Zafar,
Noor Akbar,
Afnan Jan,
Abdullatif Bin Muhsinah,
Anar Gojayev,
Ahmed Al-Harrasi
Affiliations
Asma Gul
Institute of Chemical Sciences, University of Peshawar, Peshawar, 25120, Pakistan
Sobia Ahsan Halim
Natural and Medical Sciences Research Center, University of Nizwa, P. O. Box-33, Postal Code-616, Birkat Al-Mauz, Nizwa, Sultanate of Oman
Ajmal Khan
Natural and Medical Sciences Research Center, University of Nizwa, P. O. Box-33, Postal Code-616, Birkat Al-Mauz, Nizwa, Sultanate of Oman; Corresponding author.
Rasool Khan
Institute of Chemical Sciences, University of Peshawar, Peshawar, 25120, Pakistan; Corresponding author.
P.A.N. Xian-Dao
Institute of Material Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050, China; Corresponding author.
Salman Zafar
Institute of Chemical Sciences, University of Peshawar, Peshawar, 25120, Pakistan
Noor Akbar
National Institute for Biotechnology and Genetic Engineering (NIBGE), Faisalabad, Punjab, Pakistan
Afnan Jan
Department of Biochemistry, Faculty of Medicine, Umm Al-Qura University, Makkah, Kingdom of Saudi Arabia
Abdullatif Bin Muhsinah
Department of Pharmacognosy, College of Pharmacy, King Khalid University, Abha, 62529, Kingdom of Saudi Arabia
Anar Gojayev
School of Education, General Education Program, ADA University, Ahmadbey Aghaoghlu Str. 11, Baku, AZ1008, Azerbaijan
Ahmed Al-Harrasi
Natural and Medical Sciences Research Center, University of Nizwa, P. O. Box-33, Postal Code-616, Birkat Al-Mauz, Nizwa, Sultanate of Oman; Corresponding author.
The synthesis of a new series of thiadiazine thiones including 5-(2-hydroxyethyl)-3-alkyl/aryl-1, 3, 5-thiadiazine-2-thiones (1–5), 5-(2-hydroxypropyl)-3-alkyl/aryl-1, 3, 5-thiadiazine-2-thiones (6–8), 3,5-dipropyl-1, 3, 5-thiadiazine-2-thione (9) and (2-(5-alkyl/aryl-6-thioxo-1, 3, 5-thiadiazine-3-yl) alkyl acetate/benzoate) (10–17) was accomplished via one pot reaction. The structures of the synthesized compounds were characterized through NMR and Mass spectrometry. The anti-nociceptive activity of compounds was performed on BALB/C mice by hot plate method, where compounds 3, 5 (50 μg/kg), and 8 (50, 100 μg/kg) exhibited significant effect (P < 0.01, P < 0.05) in latency time of 15, 30, and 60 min, while compounds 6 and 16 (100 μg/kg) exhibited significant effect (P < 0.01, P < 0.05) in latency time interval of 15 and 30 min. Compounds 1, 12–13, and 15 showed moderate activity. Among the tested hits, compounds 5 (17.3 ± 2.2), 11 (16.2 ± 2.1), and 8 (16.1 ± 2.1) showed significant anti-nociceptive potential. Molecular docking studies on the most active anti-nociceptive hits indicated that the activity might be attributed to the ability of the compounds to target μ-opioid receptor (μOR) effectively. Furthermore, compounds 14 and 11 showed anti-bacterial activity against Pseudomonas aeruginosa and MSRA with MIC of 40.97 and 54.77 μg/mL, respectively. In addition, the predicted ADMET profile of 5, 9, and 11 indicates that these molecules follow the drug-likeness criteria, and their activity can be enhanced through structural optimization.
