Synthesis and Antimicrobial Activity of Some 5-Substituted-3-phenyl-Nβ-(Substituted-2-oxo-2H-pyrano[2,3-b]quinoline-3-carbonyl)-1H-indole-2-carboxyhydrazide

Basavarajaiah Suliphal Devara Mathada, Mruthyunjayaswamy Bennikallu Hire Mathada
2009 Chemical and pharmaceutical bulletin  
Tuberculosis is an infection caused by Mycobacterium tuberculosis, which commonly affects the respiratory tract, i.e. lungs. 1) It is termed as "a global health emergency" by World Health Organization (WHO) in 1993 as it affects 1.7 billion people per year that is equal to one-third of the entire world population. The first line of drugs used in the treatment of tuberculosis (TB) is a combination of isoniazid, rifamycin, pyrazinamide and ethambutal. The high concentration of lipids in the cell
more » ... lipids in the cell wall of M. tuberculosis has been attributed to its resistant to antibiotics. Thus the increasing clinical importance of tuberculosis has lent additional urgency to researchers to identify new effective antimycobacterial compounds. 2) Heterocycles bearing nitrogen, sulphur and oxygen atoms in their structure constitute the core structure of a number of biologically interesting compounds. Many indole derivatives reported in the literature are known to possess varied biological activities viz., antimalarial activity, 3) antituberculosis activity 4) and COX-2 inhibitors. 5) Quinolines derivatives have attracted the attention of the chemists because of their presence in many natural products possessing significant biological activities. 6-10) Many indolo[2,3-c]isoquinolines reported from our laboratory have been found to possess bactericidal and fungicidal [11] [12] [13] activities. Earlier we have reported the synthesis of 3,5-disubstituted-N b -(2-oxobenzopyran-3-carbonyl)-1H-indole-2-carbohydrazide 14) by making use of ethyl 3-oxo-3-{2-[(5-substituted-3-phenyl-1H-indol-2-yl)carbonyl]hydrazinyl}propanoates 5a, b, which in turn were prepared by the reaction of 5-substituted-3-phenyl-1H-indole-2carbohydrazides 4a, b and diethylmalonate. In view of these findings and in continuation of our research work on indoles, 15-18) we hereby report the synthesis and antimicrobial activity of some 5-substituted-N b -(2-oxo-2H-pyrano[2,3b]quinoline-3-carbonyl)-3-phenyl-1H-indole-2-carbohydrazides 6a-j having indole and pyranoquinoline moieties in their structure with the hope getting compound with more potent antimicrobial and antituberculosis activity by making use of ethyl 3-oxo-3-{2-[(5-substituted-3-phenyl-1H-indol-2-yl)carbonyl]hydrazinyl}propanoates 5a, b and substituted-2-hydroxy-3-formylquinolines 3a-e as starting materials wherein substituted-2H-pyrano[2,3-b]quinoline moiety at-tached to b-nitrogen of 5-substituted-3-phenyl-1H-indole-2carbohydrazide at its 3-positon via carbonyl group (Chart 1). These compounds are novel and hitherto unknown. Results and Discussion Compounds 5a, b were prepared according to the reported method. 15) These compounds 5a, b when reacted with substituted-2-hydroxy-3-formyl-quinolines 3a-e in the presence of catalytic amount of piperdine in ethanol under refluxed conditions for 5 h afforded 5-substituted-N b -(2-oxo-2Hpyrano[2,3-b]quinoline-3-carbonyl)-3-phenyl-1H-indole-2carbohydrazides 6a-j in a good yield. Compound 6a in its IR spectrum showed absorption bands at 1149, 1597, 1668, 1695, 1733, 3065, 3201 and 3386 cm Ϫ1 due to C-O-C, CϭN, CϭO/CϭO/CϭO and NH/NH/NH functions respectively. Three singlets and a multiplet, observed at 9. 42, 9.71, 10.20 and 7.14-7.92 d in the 1 H-NMR spectrum of compound 6a were due to one proton of indole NH and two pro-Ethyl 3-oxo-3-{2-[(5-substituted-3-phenyl-1H-indol-2-yl)carbonyl]hydrazinyl}propanoates 5a-b were synthesized according to the literature method. These on further reaction with substituted-2-hydroxy-3-formylquinolines 3a-e yielded 5-substituted-N b b -(2-oxo-2H-pyrano[2,3-b]quinoline-3-carbonyl)-3-phenyl-1H-indole-2carbohydrazides 6a-j. Structures of the all the newly synthesized compounds were confirmed by spectral data. All these compounds have been screened for their antibacterial activity against Staphylococcus aureus, Escherichia coli and Bacillus subtilus, antifungal activity against Aspergillus niger and Candida albicans and antituberculosis activity against Mycobacterium tuberculosis (H37R v ).
doi:10.1248/cpb.57.557 pmid:19483333 fatcat:l2xzcmlz5vfdlmpixagb4nuht4