SYNTHESIS OF NOVEL γ-CARBOLINE DERIVATIVES AND THEIR IN SILICO STUDIES ON 5HT1, H1 AND CCR2 ANTAGONIST RECEPTORS
Journal Title: International Journal of Pharmacy and Pharmaceutical Sciences - Year 2014, Vol 6, Issue 10
Abstract
Objective: Synthesis of novel γ-carboline precursor 4 by using mild, inexpensive and eco friendly T3Methods: The reaction was carried out by taking mixture of 1 equiv. of phenyl hydrazine hydrochloride, 1 equiv. of N-Boc piperidone and 0.25equiv. of TP as catalyst and synthesis of γ-carbolinesulfonamides, amides and tertiary amines 5a-l from compound 4 as a key intermediate. In silico docking studies against 5HT1, H1 andCCR2 antagonist receptors of all 5a-l compounds.Results: An excellent yield of γ-carboline precursor 4 was obtained by using mild, inexpensive and eco friendly TP(50% in EtOAc) in toulene at 90 °C. After 6hr the product γ-carboline 4 was obtained by water workup followed boc deprotection byHCl in dioxane treatment. Further, the sulfonation, amidation and reductive amination were carried out to γ-carboline 4 to get derivatives of γ-carboline 5a-l. The synthesized compounds were docked against 5HT1, H1 and CCR2 antagonist receptors using AutoDock v 4.2.3Conclusion: An eco friendly procedure to prepare γ-carboline 4 using mild and inexpensive TP catalyst. Among the synthesizedcompounds, the 5b and 5c were shown three hydrogen bonding interaction having-10.1082 and-13.9105 kcal/mol of interaction energy with H1protein at the active site amino acids ARG175, TYR185 and SER128 respectively. The inhibitory constants were found to be 88.7015 and 56.2123µM respectively.3
Authors and Affiliations
E Siddalingamurthy, K. M. Mahadevan, N. M. Jagadeesh, M. N Kumara
Keywords
Related Articles
- EP ID EP579503
- DOI -
- Views 47
- Downloads 0
ANTIDYSLIPIDEMIA AND ANTIOXIDANT ACTIVITY OF ANDROGRAPHOLIDE COMPOUND FROM SAMBILOTO (ANDROGRAPHIS PANICULATA) HERB
Objective: The aim of this study was to observe the antidyslipidemic and antioxidant activity of andrographolide (AND) compound from Sambiloto (Andrographis paniculata) herb. The antidyslipidemic activity could be descri...
EFFECTIVENESS OF SPIRULINA MOUTHWASH ON REDUCTION OF DENTAL PLAQUE AND GINGIVITIS: A CLINICAL STUDY
Objective: The present study evaluated the effectiveness of Spirulina mouthwash on the reduction of dental plaque and gingivitis.Methods: A single-blind clinical trial was conducted among thirty patient’s aged 18-40 y...
CYTOTOXIC STUDIES AND PHYTOCHEMICAL ANALYSIS OF ORTHOSIPHON THYMIFLORUS (ROTH) SLEESEN
Objective: Plant-derived compounds with therapeutic effect are getting attention all over the world. Researchers are mainly targeting to ethnic and folk knowledge for the exploration of novel drug candidates. Orthosiphon...
ALTERATION IN CARBOHYDRATE METABOLISM BY SUB-ACUTE LEAD EXPOSURE: A DOSE-DEPENDENT STUDY
Objective: The study was conducted to evaluate the dose-dependent effects of sub-acute lead exposure on certain aspects of carbohydrate metabolism.Methods: Swiss albino male mice (weighing 30-35 g) were selected for the...
PRELIMINARY SURVEY OF COUNTERFEITING OF ALBENDAZOLE AND METRONIDAZOLE MARKETED IN LUBUMBASHI
Objective: Counterfeit medicines represent a major health risk in the treatment of various pathologies. They are responsible for resistance emergence in the treatment of infectious diseases. This study was conducted in o...