Novel quaternary ammonium carbapenems: 1.BETA.-Methyl-2-(5'-substituted pyrrolidinylthio)carbapenems.

Sunagawa, Makoto; Sasaki, Akira; Yamaga, Hiroshi; Shinagawa, Hisatoshi; Sumita, Yoshihiro; Nouda, Hiroshi

doi:10.7164/antibiotics.47.1337

Cited by 7 publications

(1 citation statement)

References 10 publications

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“…To improve stability, thienamycin was chemically modified over time into other more stable derivatives such as imipenem (119). Later, more stable derivatives with a broader spectrum such as biapenem, meropenem, doripenem, and ertapenem were synthesized (120)(121)(122)(123)(124)(125). Carbapenems target the PBP enzymes inhibiting peptidoglycan synthesis via crosslinking.…”

Section: Carbapenemsmentioning

confidence: 99%

Repurposing Immunomodulatory Drugs to Combat Tuberculosis

2021

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Tuberculosis (TB) is an infectious disease caused by an obligate intracellular pathogen, Mycobacterium tuberculosis (M.tb) and is responsible for the maximum number of deaths due to a single infectious agent. Current therapy for TB, Directly Observed Treatment Short-course (DOTS) comprises multiple antibiotics administered in combination for 6 months, which eliminates the bacteria and prevents the emergence of drug-resistance in patients if followed as prescribed. However, due to various limitations viz., severe toxicity, low efficacy and long duration; patients struggle to comply with the prescribed therapy, which leads to the development of drug resistance (DR). The emergence of resistance to various front-line anti-TB drugs urgently require the introduction of new TB drugs, to cure DR patients and to shorten the treatment course for both drug-susceptible and resistant populations of bacteria. However, the development of a novel drug regimen involving 2-3 new and effective drugs will require approximately 20-30 years and huge expenditure, as seen during the discovery of bedaquiline and delamanid. These limitations make the field of drug-repurposing indispensable and repurposing of pre-existing drugs licensed for other diseases has tremendous scope in anti-DR-TB therapy. These repurposed drugs target multiple pathways, thus reducing the risk of development of drug resistance. In this review, we have discussed some of the repurposed drugs that have shown very promising results against TB. The list includes sulfonamides, sulfanilamide, sulfadiazine, clofazimine, linezolid, amoxicillin/clavulanic acid, carbapenems, metformin, verapamil, fluoroquinolones, statins and NSAIDs and their mechanism of action with special emphasis on their immunomodulatory effects on the host to attain both host-directed and pathogen-targeted therapy. We have also focused on the studies involving the synergistic effect of these drugs with existing TB drugs in order to translate their potential as adjunct therapies against TB.

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Section: Carbapenemsmentioning

confidence: 99%

Repurposing Immunomodulatory Drugs to Combat Tuberculosis

2021

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β‐Lactam Antibiotics

Andreotti

Biondi

Modugno

2003

Burger's Medicinal Chemistry and Drug Discovery

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This chapter reviews the history of β‐lactams from the discovery of penicillin in 1928 to the more recently studied and the current trends in the field. The most relevant aspects related to the mechanism of action of β‐lactams are covered, and the various mechanisms of resistance to currently available β‐lactams that bacteria have adopted since the introduction of penicillin are described. A classification of β‐lactamases and their relevance in clinics is also provided. Applications of β‐lactams both in the hospital and in the community are reported, with particular attention to their pharmacokinetic properties, related side effects, and their therapeutic indications. The history and discovery of β‐lactams are described and all major classes are covered: penicillins, cephalosporins, oxacephems, carbacephems, penems, monobactams and nocardicins, carbapenems and trinems, classical (e.g., clavulanic acid, sulbactam, tazobactam), and the more recently disclosed β‐lactamase inhibitors. Several aspects related to the most recent developments in β‐lactams are also covered: new molecules active against difficult Gram‐positive strains or endowed with an antibacterial broad spectrum of action; potent orally active β‐lactams; injectable β‐lactams; and β‐lactamase inhibitors. The chapter concludes with a continuing analysis of the industry‐driven trends and the most recent new application of β‐lactams as inhibitors of protein export in bacteria. Finally, a few very interesting Web addresses and a comprehensive reference list are also provided.

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