Novel 5′-Norcarbocyclic Pyrimidine Derivatives as Antibacterial Agents

A series of novel 5′-norcarbocyclic derivatives of 5-alkoxymethyl or 5-alkyltriazolyl-methyl uracil were synthesized and the activity of the compounds evaluated against both Gram-positive and Gram-negative bacteria. The growth of Mycobacterium smegmatis was completely inhibited by the most active compounds at a MIC99 of 67 μg/mL (mc2155) and a MIC99 of 6.7–67 μg/mL (VKPM Ac 1339). Several compounds also showed the ability to inhibit the growth of attenuated strains of Mycobacterium tuberculosis ATCC 25177 (MIC99 28–61 μg/mL) and Mycobacterium bovis ATCC 35737 (MIC99 50–60 μg/mL), as well as two virulent strains of M. tuberculosis; a laboratory strain H37Rv (MIC99 20–50 μg/mL) and a clinical strain with multiple drug resistance MS-115 (MIC99 20–50 μg/mL). Transmission electron microscopy (TEM) evaluation of M. tuberculosis H37Rv bacterial cells treated with one of the compounds demonstrated destruction of the bacterial cell wall, suggesting that the mechanism of action for these compounds may be related to their interactions with bacteria cell walls.

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Antimalarial properties of orally active iron chelators

Blood ◽

10.1182/blood.v72.1.358.bloodjournal721358 ◽

1988 ◽

Vol 72 (1) ◽

pp. 358-361

Author(s):

DG Heppner ◽

PE Hallaway ◽

GJ Kontoghiorghes ◽

JW Eaton

Keyword(s):

Serum Iron ◽

Multiple Drug Resistance ◽

Iron Chelators ◽

Total Serum ◽

Multiple Drug ◽

New Class ◽

Active Iron ◽

Iron Pool ◽

Orally Active ◽

Derivatives Of

The appearance of widespread multiple drug resistance in human malaria has intensified the search for new antimalarial compounds. Metal chelators, especially those with high affinity for iron, represent one presently unexploited class of antimalarials. Unfortunately the use of previously identified chelators as antimalarials has been precluded by their toxicity and, in the case of desferrioxamine, the necessity for parenteral administration. The investigators now report that a new class of orally active iron chelators, namely the derivatives of alpha- ketohydroxypyridines (KHPs), are potent antimalarials against cultured Plasmodium falciparum. The KHPs evidently exert this effect by sequestering iron because a preformed chelator:iron complex has no antimalarial action. The pool(s) of iron being sequestered by the chelators have not been identified but may not include serum transferrin. Preincubation of human serum with KHPs followed by removal of the drug results in the removal of greater than 97% of total serum iron. Nonetheless, this serum effectively supports the growth of P falciparum cultures. Therefore the KHPs may exert antimalarial effect through chelation of erythrocytic rather than serum iron pool(s). The investigators conclude that these powerful, orally active iron chelators may form the basis of a new class of antimalarial drugs.

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Design, synthesis, docking, characterization and biological screening of novel azetidinone derivatives of nicotinic acid

Current Bioactive Compounds ◽

10.2174/1573407217666210922120323 ◽

2021 ◽

Vol 17 ◽

Author(s):

S. Amuthalakshmi Sivaperuman ◽

N. Ramalakshmi Natarajan ◽

Arunkumar Subramani ◽

Prabakaran A

Keyword(s):

Antioxidant Activity ◽

Nicotinic Acid ◽

Multiple Drug Resistance ◽

Bacterial Species ◽

Docking Studies ◽

Chemotherapeutic Agents ◽

Multiple Drug ◽

Design Synthesis ◽

Development Of Resistance ◽

Derivatives Of

Background: The prevailing multiple drug resistance among the bacterial species is alarmingly raising day to day which has become a global threat. Many infectious diseases have become untreated due to the development of resistance in bacterial species which have a considerable impact on mortality. Methods: In this present study, we aimed to synthesis a series of 12 compounds [S1-S12] which are azetidinone derivatives of nicotinic acid. The invitro antibacterial studies were performed against certain species of gram-negative and gram-positive bacteria. Molecular docking studies were performed to identify the affinity towards the target protein. The antioxidant study was also performed for the synthesized compounds. Results: All the synthesized compounds exhibited moderate to potent antibacterial activity with a MIC range of 9.8-21.6 µgmL-1, compounds were active against all tested micro-organisms. The compounds substituted with electron-donating groups like hydroxyl showed higher antioxidant activity compared to others. Docking studies were performed on the active site of DNA gyrase [PDBID: 5L3J,2XCT, 1W7Q]. Conclusion: The present study reveals the compounds synthesized exhibit very good antimicrobial activity and antioxidant activity. So, these compounds may be used as a lead for the anticancer, anti-tubercular, and other chemotherapeutic agents in future studies.

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Antimalarial properties of orally active iron chelators

Blood ◽

10.1182/blood.v72.1.358.358 ◽

1988 ◽

Vol 72 (1) ◽

pp. 358-361 ◽

Cited By ~ 44

Author(s):

DG Heppner ◽

PE Hallaway ◽

GJ Kontoghiorghes ◽

JW Eaton

Keyword(s):

Serum Iron ◽

Multiple Drug Resistance ◽

Iron Chelators ◽

Total Serum ◽

Multiple Drug ◽

New Class ◽

Active Iron ◽

Iron Pool ◽

Orally Active ◽

Derivatives Of

Abstract The appearance of widespread multiple drug resistance in human malaria has intensified the search for new antimalarial compounds. Metal chelators, especially those with high affinity for iron, represent one presently unexploited class of antimalarials. Unfortunately the use of previously identified chelators as antimalarials has been precluded by their toxicity and, in the case of desferrioxamine, the necessity for parenteral administration. The investigators now report that a new class of orally active iron chelators, namely the derivatives of alpha- ketohydroxypyridines (KHPs), are potent antimalarials against cultured Plasmodium falciparum. The KHPs evidently exert this effect by sequestering iron because a preformed chelator:iron complex has no antimalarial action. The pool(s) of iron being sequestered by the chelators have not been identified but may not include serum transferrin. Preincubation of human serum with KHPs followed by removal of the drug results in the removal of greater than 97% of total serum iron. Nonetheless, this serum effectively supports the growth of P falciparum cultures. Therefore the KHPs may exert antimalarial effect through chelation of erythrocytic rather than serum iron pool(s). The investigators conclude that these powerful, orally active iron chelators may form the basis of a new class of antimalarial drugs.

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Antisense inhibition of accA in E. coli suppressed luxS expression and increased antibiotic susceptibility

10.1101/747980 ◽

2019 ◽

Author(s):

Tatiana Hillman

Keyword(s):

Drug Resistance ◽

Antibiotic Susceptibility ◽

Multiple Drug Resistance ◽

Cell Envelope ◽

Medical Community ◽

Multi Drug Resistance ◽

Multiple Drug ◽

Bacterial Cells ◽

Inner Membrane ◽

Gram Negative

ABSTRACTBacterial multiple drug resistance is a significant issue for the medical community. Gram-negative bacteria exhibit higher rates of multi-drug resistance, partly due to the impermeability of the Gram-negative bacterial cell wall and double-membrane cell envelope, which limits the internal accumulation of antibiotic agents. The outer lipopolysaccharide membrane regulates the transport of hydrophobic molecules, while the inner phospholipid membrane controls influx of hydrophilic particles. In Escherichia coli, the gene accA produces the acetyl-CoA carboxylase transferase enzyme required for catalyzing synthesis of fatty acids and phospholipids that compose the inner membrane. To increase antibiotic susceptibility and decrease growth, this study interrupted fatty acid synthesis and disrupted the composition of the inner membrane through inhibiting the gene accA with antisense RNA. This inhibition suppressed expression of luxS, a vital virulence factor that regulates cell growth, transfers intercellular quorum-sensing signals mediated by autoinducer-2, and is necessary for biofilm formation. Bacterial cells in which accA was inhibited also displayed a greater magnitude of antibiotic susceptibility. These findings confirm accA as a potent target for developing novel antibiotics such as antimicrobial gene therapies.

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Acinetobacter With Multiple Drug Resistance Is Challenge

Internal Medicine News ◽

10.1016/s1097-8690(06)72671-3 ◽

2006 ◽

Vol 39 (2) ◽

pp. 7

Author(s):

KERRI WACHTER

Keyword(s):

Drug Resistance ◽

Multiple Drug Resistance ◽

Multiple Drug

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Surgical Site Infections - A Hospital Havoc: Retrospective Study of Surgical Site Infections in Tertiary Health Care Centre in North East India

International Journal of Innovative Research in Medical Science ◽

10.23958/ijirms/vol03-i01/09 ◽

2018 ◽

Vol 3 (01) ◽

Author(s):

V Singh ◽

A B Khyriem, W V Lyngdoh ◽

C J Lyngdoh

Keyword(s):

Surgical Site Infection ◽

Multiple Drug Resistance ◽

Surgical Site Infections ◽

Multidrug Resistant ◽

Multiple Drug ◽

Site Infection ◽

Retrospective Case ◽

Acinetobacter Baumanii ◽

Health Care Centre ◽

North East

Objectives - Surgical site infections (SSI) has turn out to be a major problem even in hospital with most modern facilities and standard protocols of pre -operative preparation and antibiotic prophylaxis. Objective of this study is to know the prevalence of surgical site infection among the postoperative patients and to identify the relationship between SSI and etiological pathogens along with their antimicrobial susceptibility at North Eastern Indira Gandhi Regional Institute of Health and Medical Sciences (NEIGRIHMS), Shillong. Methods - A retrospective case study conducted at NEIGRIHMS, among patients admitted to the surgical departments during the period between January 1st and December 31st 2016. Swabs from the surgical sites were collected under sterile conditions and standard bacteriological tests were performed for identification and appropriate statistical methods were employed to look for association between SSI and etiological pathogens. Results - Out of the 1284 samples included in the study, 192 samples showed evidence of SSI yielding an infection rate of 14.9%. The most commonly isolated bacteria were: Escherichia coli, Acinetobacter baumanii and Staphylococcus aureus, of the gram negative isolates 6.2% were multidrug resistant of which 19% were carbapenem resistant. Conclusion - SSI with multiple drug resistance strains and polymicrobial etiology reflects therapeutic failure. The outcome of the SSI surveillance in our hospital revealed that in order to decrease the incidence of SSI we would have to: a) incorporate a proper antibiotic stewardship b) conduct periodic surveillance to keep a check on SSI d) educate medical staffs regarding the prevention of surgical site infection.

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INFLUENCE OF GENOTYPIC VARIABILITY OF M. TUBERCULOSIS ON THE COURSE OF TUBERCULOSIS WITH MULTIPLE DRUG RESISTANCE

International Medical Journal ◽

10.37436/2308-5274-2020-1-15 ◽

2020 ◽

pp. 68-71

Author(s):

V. S. Krutko ◽

L. H. Nikolaieva ◽

T. V. Maistat ◽

O. A. Oparin ◽

Anton Viktorovych Rohozhyn

Keyword(s):

Clinical Laboratory ◽

Multiple Drug Resistance ◽

Multidrug Resistant ◽

Multiple Drug ◽

Genotypic Variability ◽

Intensive Phase ◽

Resistant Tuberculosis ◽

Multidrug Resistant Tuberculosis ◽

Promising Area ◽

Infection Source

Tuberculosis is infectious and socially dependent disease, being now one of the most pressing issues in practical health care. As well the usual types of tuberculosis infection, chemoresistant tuberculosis is spreading rapidly in the world. The WHO estimates that about 500,000 people on the planet are infected with M. tuberculosis, which is resistant to standard anti−tuberculosis drugs. The probability of successful treatment decreases with emergence of new genotypes of M. tuberculosis with total resistance. In the modern epidemiology of tuberculosis, it is important to identify genotypes on certain signs, allowing to address issues such as their origin, identification of the infection source, possible routes and factors of transmission, as well as to reveal cases and spread of resistance to anti−tuberculosis drugs. To evaluate the therapy efficiency of multidrug−resistant tuberculosis patients with revealed genotypic variability during treatment, 10 patients with chemoresistant pulmonary tuberculosis having M. tuberculosis genotypic variability were treated. In these patients, the clinical, laboratory and radiological dynamics of disease in intensive phase of treatment were studied. Analysis of treatment results for patients with chemoresistant tuberculosis with genotypic variability of M. tuberculosis was evaluated by the intoxication syndrome dynamics of, the timing of closure of the decay cavities and cessation of bacterial excretion. The study found that the genotypic variability of M. tuberculosis is characterized by the change of less virulent genotypes of M. tuberculosis to more virulent. Signs of intoxication have been shown to change from less virulent M. tuberculosis genotypes to M. tuberculosis Beijing genotypes. Genotypic variability of mycobacteria in hospital suggests that hospitalization in tuberculosis facilities is a risk of exogenous tuberculosis superinfection. Studying the influence of genotypic variability of M. tuberculosis on the course of multidrug−resistant tuberculosis requires more extensive research, being a very relevant and promising area in phthisiology. Key words: Mycobacterium tuberculosis, genotypic variability, VNTR−genotyping, treatment.

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