In silico study of anti-carcinogenic lysyl oxidase-like 2 inhibitors.
Lysyl oxidase homolog 2 (LOXL2), also known as lysyl oxidase-like protein 2 is recently been explored as regulator of carcinogenesis and has been shown to be involved in tumor progression and metastasis of several carcinomas. Therefore LOXL2 has been considered as potential therapeutic target. Doing so, its inhibitors as new chemotherapeutic lead molecules: 4-amino-5-(2-hydroxyphenyl)-1,2,4-triazol-3-thione (2a) and 4-(2-hydroxybenzalidine) amine-5-(2-hydroxy) phenyl-1,2,4-triazole-3-thiol (2b) are synthesized by fusion method (refluxed at 160 °C). Spectral analysis of these triazole derivatives are characterized by FTIR and NMR. Active binding sites and quality of the LOXL2 model is assessed by Ramachandran plots and finally drug-target analysis is performed by computational virtual screening tools. Compounds 2a and 2b showed optimum target binding affinity with -6.2 kcal/mol and -8.9 kcal/mol binding energies. This insilico study will add to our understanding of the drug designing and development, and to target cancer-causing proteins more precisely and quickly than before.
Department of Pharmacy, COMSATS Institute of Information Technology, Abbottabad 22060, Pakistan.
Syed Aun
SA
Muhammad
Atta-ur-Rahman School of Applied Biosciences (ASAB), National University of Sciences and Technology (NUST), Islamabad 44000, Pakistan. Electronic address: amjad_uni@yahoo.com.
Amjad
A
Ali
Department of Pharmacy, COMSATS Institute of Information Technology, Abbottabad 22060, Pakistan.
Tariq
T
Ismail
Atta-ur-Rahman School of Applied Biosciences (ASAB), National University of Sciences and Technology (NUST), Islamabad 44000, Pakistan.
Rehan
R
Zafar
Riphah Institute of Pharmaceutical Sciences (RIPS) Islamabad 44000, Pakistan.
Umair
U
Ilyas
Research Center of Modeling and Simulation (RCMS), National University of Sciences and Technology (NUST), Islamabad, Pakistan.
Jamil
J
Ahmad
D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors / Q000737:chemistry*; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry; D001665:Binding Sites; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D062105:Molecular Docking Simulation; D011485:Protein Binding; D013816:Thermodynamics; D014230:Triazoles / Q000138:chemical synthesis* / Q000737:chemistry
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D014230:Triazoles; D000594:Amino Acid Oxidoreductases; C119091:LOXL2 protein, human
Anti-cancer; Drug designing; In silico; LOXL2; Lead molecules; Triazoles