Biological activity of synthesized 5-{1-[(4-chlorophenyl)sulfonyl]piperidin-4-yl}-2-mercapto-1, 3, 4-oxadiazole derivatives demonstrated by in silico and BSA binding studies

We synthesized a series of compounds bearing pharmacologically important 1,3,4-oxadiazole and piperidine moieties. Spectral data analysis by 1H-NMR, 13C-NMR, IR and EI-MS was used to elucidate the structures of the synthesized molecules. Docking studies explained the different types of interaction of the compounds with amino acids, while bovine serum albumin (BSA) binding interactions showed their pharmacological effectiveness. Antibacterial screening of these compounds demonstrated moderate to strong activity against Salmonella typhi and Bacillus subtilis but only weak to moderate activity against the other three bacterial strains tested. Seven compounds were the most active members as acetyl cholinesterase inhibitors. All the compounds presented displayed strong inhibitory activity against urease. Compounds 7l, 7m, 7n, 7o, 7p, 7r, 7u, 7v, 7x and 7v were highly active, with respective IC50 values of 2.14±0.003, 0.63±0.001, 2.17±0.006, 1.13±0.003, 1.21±0.005, 6.28±0.003, 2.39±0.005, 2.15±0.002, 2.26±0.003 and 2.14±0.002 µM, compared to thiourea, used as the reference standard (IC50 = 21.25±0.15 µM). These new urease inhibitors could replace existing drugs after their evaluation in comprehensive in vivo studies.

Antimicrobial susceptibility patterns and phage types of Salmonella typhi from Vietnam.

A retrospective study of the patterns of antimicrobial susceptibility and phage types of 111 Salmonella typhi strains isolated in 1996 from Vietnam was carried out. The strains were tested for susceptibility to chloramphenicol, ampicillin, tetracycline, trimethoprim-sulfamethoxazole, nalidixic acid, ceftazidime, ceftriaxone and ciprofloxacin. Simultaneous resistance to chloramphenicol, ampicillin, tetracycline and trimethoprim-sulfamethoxazole were present in 84 strains (75.7%). Nalidixic acid resistance was only observed in 2 multidrug-resistant strains (1.8%). Twenty-one strains (18.9%) were completely susceptible to all drugs tested. All 111 strains were susceptible to ceftazidime, ceftriaxone and cipropfloxacin. The MIC values for chloramphenicol, ampicillin and trimethoprim-sulfamethoxazole corresponded with the results by disk diffusion method. On Vi phage-typing, 5 different phage types (28, A, D1, E1 and M1) were found in 12 strains (10.8%). However, most S. typhi strains were indistinguishable by this typing technique because they were degraded Vi-positive or untypeable Vi-positive strains (35.1% and 54.1%, respectively). There were no correlations between antimicrobial resistance patterns and phage types in the tested S. typhi strains in this study.

Phage typing, biotyping & antimicrobial resistance profile of Salmonella enterica serotype Typhi from Kolkata.

BACKGROUND & OBJECTIVE: Kolkata and its suburbs in eastern India are known to be endemic for typhoid fever. The objective of this study was to determine phage types, biotypes and antimicrobial resistance patterns of Salmonella enterica serotype Typhi isolated during the period 2003-2005 from a prospective surveillance for typhoid fever in two urban slums in Kolkata. METHODS: A total of 195 Salmonella enterica serotype Typhi isolated from blood cultures were phage typed, biotyped and tested for their antimicrobial susceptibility profile. RESULTS: Phage type E1 was the most common (60.3%) followed by phage type A among five phage types identified. Biotype I (95%) was predominant, 28 isolates were multidrug resistant (MDR) and most of the MDR strains belonged to phage type E1 and biotype I. INTERPRETATION & CONCLUSION: A single phage type and biotype were prevalent among the Salmonella enterica serotype Typhi isolates studied from Kolkata, India.

Antimicrobial susceptibility patterns of Salmonella enterica serotype typhi in eastern Nepal.

The aim of the present study was to evaluate antimicrobial susceptibility patterns with special reference to multidrug resistance, susceptibility to ciprofloxacin, and bacteriophage typing of Salmonella enterica serotype Typhi isolated from blood sent for culture in a tertiary-care teaching hospital in eastern Nepal during January 2000-December 2004. In total, 132 strains of S. enterica Typhi, isolated from 2,568 blood culture samples collected from cases of suspected enteric fever, were tested for susceptibility to commonly-used antimicrobials by the disc-diffusion method. There were 35 multidrug-resistant strains. None of the isolates were resistant to ciprofloxacin. Of 52 isolates tested for minimum inhibitory concentration (MIC) of ciprofloxacin, 36 (69.23%) showed reduced susceptibility (MIC >0.25 mg/L). Of 112 strains tested for nalidixic acid susceptibility, 86 (76%) were resistant. Strains with reduced susceptibility to ciprofloxacin and resistance to nalidixic acid could be correlated. The commonest phage type was El. Nalidixic acid susceptibility could be a useful screening test for the detection of decreased susceptibility of S. Typhi to ciprofloxacin, a drug which is commonly used even for minor ailments in this area.

Changing trends in the antibiograms of Salmonella isolates at a tertiary care hospital in Hyderabad.

The present study was undertaken to compare the changing trends of antibiograms of Salmonella enterica serovar Typhi and Salmonella enterica serovar Paratyphi A isolates. A total of 80 isolates of salmonella obtained from blood cultures between 2001-2004 were included in the study. Identification and antibiotic sensitivities of the isolates were performed by using mini API (bio Merieux, France). Sixty isolates were identified as Salmonella enterica serovar Typhi and 20 were identified as Salmonella enterica serovar Paratyphi A. More than 67% of S.typhi and 80% of S.paratyphi A isolates were sensitive to chloramphenicol. Sensitivity of S.typhi isolates to cephalosporins was found to have increased from 2001-2004 while that of S.paratyphi A showed a decline. With increasing resistance to ciprofloxacin and the possibility of re-emergence of sensitivity to chloramphenicol, the policy of empirical treatment of enteric fever needs to be rationalized.

Increase in minimum inhibitory concentration to quinolones and ceftriaxone in salmonellae causing enteric fever.

Multidrug resistance among Salmonella typhi is well known. Reports of treatment failure in enteric fever with Ciprofloxacin made us undertake this study to determine the antibiotic susceptibility pattern of S. typhi and S. paratyphi A isolated from typhoid bacteremia cases, by disc diffusion and MIC by broth dilution method. A total of 50 strains were tested, 48 of Salmonella typhi and 2 of S. paratyphi A. The disc diffusion method was done using ampicillin, chloramphenicol, cotrimoxazole, tetracycline, ciprofloxacin, ofloxacin, cefuroxime and ceftriaxone as antibiotics. The MIC was performed using ciproloxacin, ofloxacin and ceftriaxone based on standard procedure. ACCOT resistance as determined by disc diffusion method was seen in 68% of isolates. All the strains remained susceptible to flouroquinolones cephalosporins and aminoglycosides. The MIC of ciprofloxacin, ofloxacin and ceftriaxone were in the recommended range of susceptibility as given by NCCLS, 14 (28%) strains had MIC of ciprofloxacin greater than 0.5 ug/ml with 4 strains having an MIC of 1.56 ug/ml; 25 (50%) strains had MIC of ofloxacin greater than 0.5 ug/ml and 20 (40%) strains had MIC of ceftriaxone greater than 0.5 ug/ml. The high levels of MIC of ciprofloxacin may account for treatment failure cases. The rising levels of MIC of ofloxacin and ceftriaxone in S. typhi and S. paratyphi is also of concern. We document here the emergence of high levels of MIC not only to ciprofloxacin, but also ofloxacin and ceftriaxone in S. typhi and S. paratyphi A. We recommend that MIC levels of ofloxacin and ceftriaxone should be monitored along with ciprofloxacin in treatment failure cases of enteric fever.

Antibacterial activity of black tea (Camelia sinensis) extract against Salmonella serotypes causing enteric fever.

Alcoholic extract of black tea (Camelia sinensis) was assayed for its antibacterial activity against Salmonella serotypes causing enteric fever viz., Salmonella typhi and Salmonella paratyphi A. While all strains of S. paratyphi A tested were found sensitive, only 42.19% of S. typhi strains were inhibited by this extract. Further minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of black tea extract against S. paratyphi A was less compared with that against S. typhi.

Differentiation of Salmonella typhi strains by ribosomal RNA gene restriction patterns.

Owing to the limited value of phage typing to determine the epidemiological association of Salmonella typhi (S. typhi) strains isolated from the source of typhoid fever, we analyzed ribosomal RNA (rRNA) gene restriction patterns to differentiate the independently isolated strains of identical phage type. The data showed that the restriction patterns of PstI was most polymorphic among four enzymes (BamHI, EcoRI, PstI, and SmaI) used, which revealed 13 types among 25 strains belonged to 4 phage types, 1 untypable and 2 not-determined strains. Total 25 strains of S. typhi were divided into 15 combination types by the rRNA restriction patterns with three enzymes (BamHI, PstI, and SmaI).

Current status of drug resistance & phage types of Salmonella typhi in India.

A total of 11391 strains of S. typhi were received at the National Salmonella Phage Typing Centre at New Delhi during January 1990- August 1992, from various regions of India. Of these, 39.7 per cent were from north India, 37.5 per cent from central India and 22.8 per cent from south India. 64.5 per cent of S. typhi were found to be multidrug resistant (MDR), maximum resistance being observed in 1991 (71.6%) while it was least in 1990 (50.05%). There was a slight decline in the percentage of MDR strains in 1992. Region-wise analysis of the resistant strains showed maximum number in central India (71.32%), whereas it was least in the south (55.2%); 62.34 per cent of strains received from north India were MDR. Irrespective of the year or region, the predominant resistance pattern remained AMCSXTTE. The commonest phage type was E1, followed by 0 and A. This pattern was also seen in the MDR S. typhi. Certain degraded Vi strains, untypable Vi strains and Vi negative strains were also multidrug-resistant. An important change observed in this study was that a small number of strains belonging to phage types C1, K1, 28, 40, 41 and 42 which were always sensitive earlier, had developed multidrug resistance. Small outbreaks due to one phage type (e.g., 28 and 51) were short lived and subsided spontaneously. More diversity of phage types was observed in north India as compared to central and south India.

Multidrug resistant Salmonella typhi in Calicut, south India.

Eighty S. typhi strains isolated during the period of one year (July 1989 to June 1990) were tested for susceptibility to chloramphenicol, ampicillin, cotrimoxazole, gentamicin, kanamycin, cefazolin, furazolidone and ciprofloxacin. Determination of minimum inhibitory concentration (MIC) by tube dilution method showed that the multiply resistant S. typhi strains were resistant to chloramphenicol and ampicillin up to a concentration of 1000 micrograms/ml. MIC of sulphamethoxazole was found to be 800 micrograms/ml and trimethoprim 160 micrograms/ml. The presence of R plasmid was demonstrated by resistance transfer experiments using Esch. coli K12 (F-Lac+Nal-) as the recipient. On phage typing, most of the multiresistant S. typhi isolates were found to belong to phage type E1.

Antibiogram, phage types & biotypes of Salmonella typhi isolated in Nagpur.

S. typhi was isolated from 241 patients of pyrexia between July 1990 and March 1991. Multiple drug resistance was observed in 220 (91.3%) strains, the commonest pattern of drug resistance being ACCoT (49.4%). Predominance of phage type E1 in 196 (81.3%) strains and biotype I in 225 (93.4%) strains was observed. All ACCoT strains belonged to phage type E1 and all strains of phage type E1 belonged to biotype I.

A mouse monoclonal antibody to Vi antigen & its usefulness in the serotyping of Salmonella.

Three IgM monoclonal antibodies (MoAb) designated as MK2, MK3 and MK5 and specific for the Vi antigen of Salmonella typhi have been produced. These antibodies recognise the epitope involving the O-acetyl group of Vi antigen. In slide agglutination tests, these MoAb's agglutinated all 11 isolates of S. typhi but not the other Gram negative bacteria. This selective reactivity makes them better reagents for the identification of S. typhi than the conventional polyclonal antiserum.