Nishith Kumar Pal

New quinoline derivatives: synthesis and investigation of antibacterial and antituberculosis properties.

Four new series of quinoline derivatives were synthesized starting from 2-trifluoromethyl aniline through multi-step reactions. In the reaction sequence, substituted aniline was cyclized to 4-hydroxy quinoline 1, which was then transformed to 4-chloro-2,8-bis(trifluoromethyl)quinoline 2. The key scaffold 4-hydrazinyl-2,8-bis(trifluoromethyl)quinoline 3, obtained from the compound 2, was successfully converted to target quinoline derivatives, viz. hydrazones 4a-t, ureas 5a-e, thioureas 6a-c and pyrazoles 7a-d, in good yields. The newly synthesized title compounds were evaluated for their in vitro antibacterial activity against Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa and Klebsiella pneumoniae (recultured) and antituberculosis activity against Mycobacterium tuberculosis H(37)Rv and MDR-TB. Preliminary results indicated that most of the hydrazone derivatives demonstrated very good antibacterial and antituberculosis activities while other derivatives showed moderate activity.

New quinolin-4-yl-1,2,3-triazoles carrying amides, sulphonamides and amidopiperazines as potential antitubercular agents

Three new series of quinoline-4-yl-1,2,3-triazoles carrying amides, sulphonamides and amidopiperazines were synthesized through multi-step reactions. The required intermediate, [1-(6-methoxy-2-methylquinolin-4-yl)-1H-1,2,3-triazol-4-yl]methanol (2) was prepared by treating 4-azido-6-methoxy-2-methylquinoline (1) with propargyl alcohol. Three different series of compounds were synthesized from this intermediate. All the newly synthesized compounds were characterized by spectral and elemental analyses. The structure of 2 was confirmed by X-ray crystallographic study. Further, the title compounds were evaluated for their in vitro anti-bacterial activity against five different bacterial strains and antimycobacterial activity against Mycobacterium tuberculosis H37Rv, Mycobacterium smegmatis (ATCC 19420) and Mycobacterium fortuitum (ATCC 19542). Title compounds, 6a, 6d, 6i, 6j, 7e, 10a and 10i were found to be active against Mycobacterium tuberculosis H37Rv strain and could be lead molecules of interest.

Design and synthesis of some new quinoline-3-carbohydrazone derivatives as potential antimycobacterial agents

A series of 26 new quinoline derivatives carrying active pharmacophores has been synthesized and evaluated for their in vitro antituberculosis activity against Mycobacterium tuberculosis H37Rv (MTB), Mycobacterium smegmatis (MC(2)), and Mycobacterium fortuitum following the broth micro dilution assay method. Compounds 13e, 13i, 13k, 14a, 14c, 14i, and 14k exhibited significant minimum inhibition concentrations, when compared with first line drugs isoniazid (INH) and rifampicin (RIF) and could be ideally suited for further modifications to obtain more efficacious compounds in the fight against multi-drug resistant tuberculosis.

Design, synthesis and docking studies of new quinoline-3-carbohydrazide derivatives as antitubercular agents.

Three new series of 4-hydroxy-8-trifluoromethyl-quinoline derivatives were synthesized through multi step reactions. All the newly synthesized compounds were characterized by spectral and elemental analyses. The structure of 5j was evidenced by X-ray crystallographic study. The newly synthesized title compounds were evaluated for their antimicrobial activities including antimycobacterial activity. Amongst the tested compounds, 5b, 5e, 5h, 5j, 6c and 7c displayed promising antimicrobial activity. The mode of action of these active compounds was carried out by docking of receptor enoyl-ACP reductase with newly synthesized candidate ligands, 5b, 5e, 5h, 5j and 6c.

Cholera: a great global concern.

Cholera, caused by the infection of toxigenic Vibrio cholerae (V. cholerae) to humans, is a life threatening diarrheal disease with epidemic and pandemic potential. The V. cholerae, both O1 and O139 serogroups, produce a potent enterotoxin (cholera toxin) responsible for the lethal symptoms of the disease. The O1 serogroup has two biotypes (phenotypes), classical and El Tor; each of which has two major serotypes (based on antigenic responses), Ogawa and Inaba and the extremely rare Hikojima. V. cholerae O1 strains interconvert and switch between the Ogawa and Inaba serotypes. Fluid and electrolyte replacement is the mainstay of treatment of cholera patients; the severe cases require antibiotic treatment to reduce the duration of illness and replacement of fluid intake. The antibiotic therapy currently has faced difficulties due to the rapid emergence and spread of multidrug resistant V. cholerae causing several outbreaks in the globe. Currently, cholera has been becoming endemic in an increasing number of geographical areas, reflecting a failure in implementation of control measures. However, the current safe oral vaccines lower the number of resistant infections and could thus represent an effective intervention measure to control antibiotic resistance in cholera. Overall, the priorities for cholera control remain public health interventions through improved drinking water, sanitation, surveillance and access to health care facilities, and further development of safe, effective and appropriate vaccines. Thus, this review describes the facts and phenomena related to the disease cholera, which is still a great threat mainly to the developing countries, and hence a grave global concern too.

Antibacterial activity of honey against clinical isolates of Escherichia coli,Pseudomonas aeruginosa and Salmonella enterica serovar Typhi

Abstract Objective To ascertain the potential antibacterial activity of honey against clinical isolates of Escherichia coli (E. coli), Pseudomonas aeruginosa (P. aeruginosa) and Salmonella enterica serovar Typhi (S. enterica serovar Typhi ) by in vitro methods. Methods The partial inhibitory concentration (PIC), minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values of the autoclaved honey (extracted from Apis indica hive by indigenous method) were determined for S. enterica serovar Typhi ( n =8; from blood cultute), E. coli ( n =5; from urine culture) and P. aeruginosa ( n =5; from pus culture) isolates by in vitro methods. Results The PICs of the honey tested for the isolates ranged 0.50%-1.25 % (v/v) for S. enterica serovar Typhi, 0.75%-1.50% (v/v) for E. coli and 1.00%-1.25 % (v/v) for P. aeruginosa , while the MICs ranged 1.75%–3.00% (v/v), 3.00%-3.50% (v/v) and 3.50% (v/v), respectively. The P. aeruginosa and E. coli isolates had MBC value of 4.00% (v/v); the S. enterica serovar Typhi showed MBCs in between 3.00% and 3.50% (v/v). The bactericidal activity of honey was achieved at concentration 3.00% (v/v) for S. enterica serovar Typhi and E. coli , and at 3.50% (v/v) for P. aeruginosa . Conclusions The excellent antibacterial activity of honey against clinical bacterial isolates indicates the usefulness of honey in clinical practice against bacterial infection.

Synergistic anti–Staphylococcus aureus activity of amoxicillin in combination with Emblica officinalis and Nymphae odorata extracts

To evaluate the antibacterial activity of Emblica officinalis Gaertn (E. officinalis; Family: Euphorbiaceae) seed and Nymphae odorata Aiton (N. odorata; Family: Nymphaeaceae) stamen extracts, alone and in combination, and in combination with amoxicillin (Ax) against Staphylococcus aureus (S. aureus). 1eiliods: Antibacterial activity of ethanolic extracts of amla, E. officinalis, seed (AMS; 500μg) and sapla, N. odorata, stamen (SAP; 500μg) for 12 methicillin-resistant S. aureus (MRSA) isolates was determined following agar diffusion; in order to assess the combined antibacterial activity, AMS (250μg) plus SAP (250μg) were considered. The Ax (10μg) activity alone and in combination with AMS (250μg), and SAP (250μg) was determined by disk diffusion. The zone diameters of inhibition (ZDIs) for the agents were recorded, and growth inhibitory indices (Gus) were calculated. Results: The MRSA isolates (n=12) had AMS (500 p g) and SAP (500μg) ZDIs of 12-19 mm and 21-24 mm, respectively. The ZDIs (range 24-27 mm) increased by 3-4 mm due to combined action of AMS (250μg) and SAP (250μg) indicating synergy between extracts for MRSA (GII 0.634-0.742). The MRSA isolates were resistant to Ax (ZDI: 8-11 mm), which in combination with AMS and SAP had synergistic effect, both due to increased ZDI [mean±SD(3.5±0.577)mm] and GII (0.631-0.894). Conclusions: The data suggest that the plants, E. officinalis and N. odorata alone or in combination, are promising in the development of phytomedicines, which may be used, alone or in combination with the antibiotic, Ax, against MRSA infection.

In vitro antibacterial potential of Eugenia jambolana seed extracts against multidrug-resistant human bacterial pathogens.

The present study was carried out to evaluate the possible in vitro antibacterial potential of extracts of Eugenia jambolana seeds against multidrug-resistant human bacterial pathogens. Agar well diffusion and microbroth dilution assay methods were used for antibacterial susceptibility testing. Kill-kinetics study was done to know the rate and extent of bacterial killing. Phytochemical analysis and TLC-bioautography were performed by colour tests to characterize the putative compounds responsible for this antibacterial activity. Cytotoxic potential was evaluated on human erythrocytes by haemolytic assay method and acute oral toxicity study was done in mice. The plant extracts demonstrated varying degrees of strain specific antibacterial activity against all the test isolates. Further, ethyl acetate fraction obtained from fractionation of most active ethanol extract showed maximum antibacterial effect against all the test isolates. Phytochemical analysis and TLC-bioautography of ethyl acetate fraction revealed that phenolics were the major active phytoconstituents. Ethyl acetate fraction also demonstrated no haemolytic activity on human erythrocytes and no gross behavioural changes as well as toxic symptoms were observed in mice at recommended dosage level. The results provide justification for the use of E. jambolana in folk medicine to treat various infectious diseases and may contribute to the development of novel antimicrobial agents for the treatment of infections caused by these drug-resistant bacterial pathogens.

Alteration of serum inflammatory cytokines in active pulmonary tuberculosis following anti-tuberculosis drug therapy

Active pulmonary tuberculosis (APTB) is associated with a failure of the host immune system to control the invading Mycobacterium tuberculosis (Mtb). The objective of this study was to quantify and assess the role of serum inflammatory cytokines in active pulmonary tuberculosis patients following anti-tuberculosis drug (ATD) therapy. Blood samples were collected from APTB patients and normal healthy subjects (NHS) (total n=204) at baseline and 2, 4 and 6 months post-therapy and the abundance of serum inflammatory cytokines were measured by cytokine specific ELISA. Compared to NHS, APTB patients at baseline had higher levels of serum pro-inflammatory cytokines IL-12p40 (P<0.001), IFN-γ (P<0.001), TNF-α (P<0.01), IL-1β (P<0.001) and IL-6 (P<0.001) and anti-inflammatory cytokines IL-10 (P<0.001) and TGF-β1 (P<0.001) while there was no change in the level of IL-4. In APTB patients, the serum levels of IFN-γ, TNF-α, IL-6 and TGF-β1 directly relate to the bacterial load while the TNF-α, IL-1β, IL-6 and TGF-β1 relate to radiological severity. At baseline, the IL-6 level in NHS and APTB patients differed most and following ATD therapy, this level rapidly decreased and stabilized by 4-month in APTB patients. It is concluded that a subtle reduction in the serum level of IL-6 of the APTB patients following ATD therapy might play a vital role in immune-protection of the host against Mtb infection and hence the serum IL-6 level can be a useful marker to diagnose the effectiveness of therapy in the patients.

In Vitro Antibacterial Activity of three Indian Spices Against Methicillin-Resistant Staphylococcus aureus.

OBJECTIVE To explore the in vitro antibacterial activity of ethanolic extracts of cinnamon (Cinnamomum zeylanicum; CIN), clove (Syzygium aromaticum, CLV) and cumin (Cuminum cyminum, CMN) against clinical isolates of methicillin resistant Staphylococcus aureus (MRSA), from Kolkata, India. METHODS The CIN, CLV and CMN were tested for their antibacterial activity against MRSA by in vitro methods. Minimum inhibitory concentration (MIC) values of the three extracts were determined, and time-kill studies were performed in order to investigate the bactericidal activity of the extracts (at the MIC level) for the isolates. The killing efficacy of the extracts was determined at various concentrations. RESULTS The zone diameter of inhibition (ZDI) obtained due to CIN, CLV and CMN ranged between 22-27 mm, 19-23 mm and 9-15 mm, respectively; while the MICs, for the isolates, were in the range of 64-256, 64-512 and 128-512 µg/ml, respectively. When tested for their MIC levels; the CIN and CLV were found to be bactericidal after 6 hrs of incubation, while CMN showed bactericidal activity after 24 hrs. However, when tested at various concentrations; CIN, CLV and CMN displayed bactericidal activity against S. aureus, after 24 hrs of incubation, at 200, 200 and 300 µg/ml, respectively. CONCLUSION The C. zeylanicum and S. aromaticum showed the strongest in vitro antibacterial activity followed by C. cyminum against MRSA, and such findings could be considered a valuable support in the treatment of infection and may contribute to the development of potential antimicrobial agents for inclusion in anti- S. aureus regimens.