title: Synthesis of BF₃ catalyzed Mannich derivatives with excellent ee from phenylpropanolamine, study of their antimicrobial activity and molecular docking.
abstract: Antimicrobial agents 4a-g and 5a-g with very good potency were synthesized with 100% ee from phenylpropanolamine (norephedrine) by BF3 catalyzed three components one pot Mannich reaction in good yields. Obtained compounds were characterized using spectral techniques. Antimicrobial study of these compounds revealed a good to very high potential activity against tested microbes when compared to standard antimicrobial drugs streptomycin and ketoconazole. These synthesized compounds exhibited significant minimum inhibitory concentration (MIC) values against Gram positive and Gram negative bacteria. Amongst compound 4b, 4c, 4d, 4e, 5a, and 5e exhibited very high potent MIC values against tested twelve bacteria and three fungi when compared to control. When subjected to molecular docking, in silico studies revealed significant binding energies ranging from -7.06 to -8.90 kcal/mol for all obtained compounds towards target receptor DNA topoisomerase IV and amongst compounds 4b and 4d have shown maximum binding energies 8.70 and 8.90 kcal/mol, respectively.
authors: Organic Chemistry Division, CSIR-Central Leather Research Institute, Adyar, Chennai 600020, Tamil Nadu, India; R&D Center, Malladi Drugs & Pharmaceuticals Ltd, Poonamalle, Chennai 600124, Tamil Nadu, India.
authors: K
authors: K
authors: Chennakesava Rao
authors: R&D Center, Malladi Drugs & Pharmaceuticals Ltd, Poonamalle, Chennai 600124, Tamil Nadu, India.
authors: K
authors: K
authors: Easwaramoorthi
authors: Organic Chemistry Division, CSIR-Central Leather Research Institute, Adyar, Chennai 600020, Tamil Nadu, India.
authors: Y
authors: Y
authors: Arun
authors: Department of Hematology, Fujita Health University, 1-98, Dengakugakubo, Kutsukake-cho, Toyoake, Aichi 470-1192, Japan.
authors: C
authors: C
authors: Balachandran
authors: R&D Center, Malladi Drugs & Pharmaceuticals Ltd, Poonamalle, Chennai 600124, Tamil Nadu, India.
authors: K S
authors: KS
authors: Muralidhara Rao
authors: Department of Chemistry, Anna University, Guindy, Chennai 600020, Tamil Nadu, India.
authors: M
authors: M
authors: Govindhan
authors: Department of Hematology, Fujita Health University, 1-98, Dengakugakubo, Kutsukake-cho, Toyoake, Aichi 470-1192, Japan.
authors: Nobuhiko
authors: N
authors: Emi
authors: R&D Center, Malladi Drugs & Pharmaceuticals Ltd, Poonamalle, Chennai 600124, Tamil Nadu, India.
authors: T
authors: T
authors: Prakasam
authors: Organic Chemistry Division, CSIR-Central Leather Research Institute, Adyar, Chennai 600020, Tamil Nadu, India. Electronic address: ptperumal@gmail.com.
authors: P T
authors: PT
authors: Perumal
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001880:Boranes; D002384:Catalysis; D004305:Dose-Response Relationship, Drug; D006090:Gram-Negative Bacteria / Q000187:drug effects*; D006094:Gram-Positive Bacteria / Q000187:drug effects*; D008352:Mannich Bases / Q000737:chemistry* / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D010665:Phenylpropanolamine / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D001880:Boranes; D008352:Mannich Bases; D010665:Phenylpropanolamine; C021274:boron trifluoride
keywords: DNA topoisomerase IV; Lewis acid catalyzed Mannich reaction; Minimum inhibitory concentration; Phenylpropanolamine; Zone of inhibition