ABSTRACT
A series of N-substituted morpholines 2-20 was synthesised by reacting various acid chlorides and alkyl halides with morpholine (1). All of the synthesised compounds 2-20 were screened for their leishmanicidal effects using amphotericin B (IC(50) = 0.24 microg L(-1)) and pentamidine (IC(50) = 2.56 microg mL(-1)) as standards and a structure-activity relationship (SAR) study was established. The compounds 2 (IC(50) = 48 microg mL(-1)), 3 (IC(50) = 30.0 microg mL(-1)), 10 (IC(50) = 41.0 microg mL(-1)), 15 (IC(50) = 33.0 microg mL(-1)), 16 (IC(50) = 35.0 microg mL(-1)) and 20 (IC(50) = 47.0 microg mL(-1)) showed weak leishmanicidal activities.
Subject(s)
Antiprotozoal Agents/chemical synthesis , Antiprotozoal Agents/pharmacology , Morpholines/chemical synthesis , Morpholines/pharmacology , Animals , Leishmania major/drug effects , StereoisomerismABSTRACT
A variety of piperidines (2-12, 14-26) with variable substituents at N-atoms have been synthesized and evaluated as urease inhibitors. The synthesized compounds showed varying degree of urease inhibitory activity ranging from 31.97 to 254 microM. The size and electron-donating or -withdrawing effects of substituents influence the activity, which lead to the formation of urease inhibitors.
Subject(s)
Enzyme Inhibitors/chemistry , Piperidines/chemistry , Urease/antagonists & inhibitors , Enzyme Inhibitors/chemical synthesis , Enzyme Inhibitors/pharmacology , Inhibitory Concentration 50 , Magnetic Resonance Spectroscopy , Molecular Structure , Piperidines/chemical synthesis , Piperidines/pharmacology , Spectrometry, Mass, Electrospray IonizationABSTRACT
Twenty-eight tetraketones (1-28) with variable substituents at C-7 were synthesized and evaluated as tyrosinase inhibitors. Remarkably compounds 25 (IC(50)=2.06 microM), 11 (IC(50)=2.09 microM), 15 (IC(50)=2.61 microM), and 27 (IC(50)=3.19 microM) were found to be the most active compounds of the series, even better than both standards kojic acid (IC(50)=16.67 microM) and L-mimosine (IC(50)=3.68 microM). This study may lead to the discovery of therapeutically potent agents against clinically very important dermatological disorders including hyperpigmentation as well as skin melanoma.
Subject(s)
Enzyme Inhibitors/pharmacology , Ketones/pharmacology , Monophenol Monooxygenase/antagonists & inhibitors , Spectrum Analysis/methodsABSTRACT
The microwave-assisted synthesis and characterization of the ten new sildenafil (Viagra; 1) analogues 6-15 are described. A detailed structure-activity-relationship (SAR) study revealed that compounds 10 (= 4-ethoxy-N-hydroxy-3-(7-methoxy-1-methyl-3-propyl-1H-pyrazolo[4,3-d]pyrimidin-5-yl)benzenesulfonamide) and 12 (= S-(2-hydroxyethyl) 4-ethoxy-3-(7-methoxy-1-methyl-3-propyl-1H-pyrazolo[4,3-d]pyrimidin-5-yl)benzenesulfonothioate) are extremely potent mushroom tyrosinase inhibitors, with IC50 values (3.59 and 2.15 microM, resp.) below those of the standard inhibitors L-mimosine and kojic acid (IC50 = 3.68 and 16.67 microM, resp.). Compounds 10 and 12 are, thus, the currently most-effective inhibitors of tyrosinase, and bear great potential to be used for the treatment of various skin disorders such as hyperpigmentation, which is associated with high production of melanocytes.
Subject(s)
Monophenol Monooxygenase/antagonists & inhibitors , Piperazines/chemistry , Piperazines/pharmacology , Molecular Structure , Purines , Sildenafil Citrate , Structure-Activity Relationship , SulfonesABSTRACT
A variety of biscoumarins (1-21) with variable substituents at C-11 were synthesized with an improved method and evaluated as urease inhibitors. The synthesized compounds showed varying degree of urease inhibitory activity ranging from 15.06-91.35 microM. The size and electron donating or withdrawing effects of substituents influenced the activity, which lead to the urease inhibitors.
