Pharmaceutical & Medicinal Organic Chemistry - Anti-Infectives and Beta-Lactam Antibiotics

Flashcards covering key vocabulary related to anti-infectives, alcohols, ethylene oxide, phenolics, oxidizing agents, halogen-containing compounds, cationic surfactants, dyes, mercury-containing compounds, preservatives, and beta-lactam antibiotics.

Antiseptics

Compounds that either kill (Cidal) or prevent growth (Static) of microorganisms when applied to living tissues.

Disinfection

Prevent the transmission of infection to inanimate objects

Decontamination

The combination of processes that removes or destroys contamination to prevent an infectious agent or contamination from reaching a susceptible site.

Sanitation

A set of practices or procedures to ensure that good hygiene is being maintained to prevent disease due to waste.

Sterilization

Processes that will result in a surface/object being free from any microorganisms or viruses

Pasteurization

Processes of food preservation that eliminate pathogens by using gentle heat in order to extend shelf life.

Ideal Disinfectant

Rapid lethal action against microorganisms including spores, good penetration in organic matter, not inactivated by living tissues, and non-corrosive.

Effectivity of Alcohol

Increases as the number of carbons increases, however up to 8 carbons only

Denatured Alcohol

Composed of Benzene + Methanol (AKA Wood Alcohol).

Dehydrated Alcohol

99% Ethanol, obtained via absolute azeotropic distillation of ethanol and benzene

Metabolism of Ethanol

Series of Oxidation

Isopropyl Alcohol

AKA Rubbing Alcohol

Epoxide

CYCLIC ETHERS (R-O-R) or Ethers in Ring Form

Phenol coefficient

Measurement of a disinfectant’s effectiveness compared to Phenol

Low Concentration of Phenols

Our proteins have three types of structures: Primary, Secondary, and Tertiary

High Concentration of Phenols

Achieves Lysis, when a cell bursts due to a high concentration of phenol, which disrupts its structure and function

Joseph Lister

Observed that patients often developed infections after surgery because surgeons did not properly wash their hands and introduce antiseptic techniques

p-Chlorophenol

The chlorine is attached at the para position, Enhances its activity, and is used in combination with camphor in liquid petrolatum

Hexachlorophene

Insoluble in water but soluble in alcohol and other organic solvents. Structure is a Biphenol Ring (2 phenol rings).

Cresol

Cresols are a group of substances wherein their R-group is methyl, and are obtained from coal tar in petroleum via alkaline extraction or distillation

Thymol

A volatile oil from Thyme (Thymus vulgaris). Mild fungicidal traditionally used as an antifungal, particularly for tinea infections.

Eugenol

Most common source is clove oil (Syzygium aromaticum), Local anesthetic and antiseptic property; Component in Toothache Drops and Mouthwashes

Keratolytic agent

Help remove dead skin cells by speeding up the skin's natural shedding process and aiding in skin renewal and recovery

Liberation of Nascent Oxygen

Short-lived, highly reactive form of oxygen.

Carbamine peroxide

Complex that contains UREA and HYDROGEN PEROXIDE

Mechanism of Action (Keratolytic)

Induces cell proliferation (epithelial), leading to sloughing and repair, and results in loosening and removal of dead skin cells

Iodine and Iodophors

Preparations containing Iodine are BACTERICIDAL

Iodophors

Preparation that releases iodine, and utilizes non-ionic surfactant

Cationic Surfactants

Contains a POSITIVELY CHARGED HEAD, which interacts with the Negatively Charged Surfaces of the Cell Membrane

Benzalkonium chloride

emulsifying agent by mixing two immiscible liquids

Methylbenzethonium chloride

Treatment of DIAPER RASH in infants caused by Candida and is a component of Diaparene

Dyes Effectiveness

Dyes should exist in positively charged form for them to exert antiseptic properties

Mercury- Containing Compounds Mechanism of Action

Mercury BINDS to microbial enzymes, particularly those containing Sulfhydryl Group (-SH), and reacts to form a COVALENT BOND (irreversible) R-S-HG-R Group

Preservatives Effectivity

Effective in LOW CONCENTRATIONS against ALL POSSIBLE MICROORGANISMS

Parabens General Structure & Structure-Activity Relationship

Para-Substituted Ester Group in Phenol Ring and has R-Group Substituted by Alkyl Groups

Discovery of Penicillins: Sir Alexander Fleming

Developed penicillin, the world’s first antibiotic, after noticing a mold (Penicillium notatum) inhibited bacterial growth in a petri dish

Beta-Lactam Antibiotics Members

Classification of Antibiotics that Posses the B-lactam Ring

PBP

Enzymes that biosynthesize the bacterial cell wall such as Transpeptidase

General Structure

The pharmacophore refers to the core structure responsible for the drug's activity, which in the case of penicillin is the beta-lactam ring

Bicyclic Ring System: PENAM RING

Bicyclic ring system of penicillin with 6-Aminopenicillanic acid (6-APA)

Carbonyl Group

The carbonyl group attaches to the hydroxyl group of serine in the transpeptidase enzyme.

Due to the strained angle of the ring

The group confers an Electrophilic nature due to lack of resonance of electrons within the ring.

Thiazolidine Ring

Five-membered nitrogen-saturated ring

Cis-Stereochemistry

Essential configuration for binding to Transpeptidases

(+) Electron Withdrawing Group

Draws Electrons Away from the carbonyl carbon = Nucleophilic Properties (electron-rich)

(+) Bulky Groups

Provides Steric Hindrance (steric strain) to Alpha-Carbon

(+) Polar or Ionized Functional Groups

Should be attached to the Alpha-carbon and Increases Hydrophilic Properties of Structure

Natural Penicillins Sources

Benzylpenicillin (Pen G) and Phenoxymethylpenicillin (Pen V)

Benzylpenicillin Disadvantage

Acid-labile and Poor intestinal absorption, Route of Administration: Parenteral (IM or IV)

Potassium salt of Phenoxymethylpenicillin

Achieves higher resistance to stomach acids

Methicillin Advantage

Resistant to penicillinase found in Staphylococci and Bacillus cereus

Nafcillin

Bulky Groups with Naphthalene Side Chain. Use for the treatment of infections caused by: Staphylococcus spp.

Ampicillin Structure

Amino Group substituted at the Alpha-Carbon (Benyllic Carbon). Lacks Steric Hindrance

The effect of Subactam as a suicide drug

It spares the ampicillin from the effects of beta-lactamase.

Discovery of Cephalosporins: Giuseppe Brotzu

Discovered in 1945 of a mold isolated from sewage outfall.

Mode of Action of Cephalosporins

Beta-Lactam Antibiotics, Cell Wall Synthesis Inhibitor & Bactericidal

Bicyclic Ring System: CEPHEM RING

Fused Beta-Lactam and Dihydrothiazine Ring or cephalosporin ring.

Position 3 Substituent

Substitution will improve PHARMACOKINETIC PROPERTIES

Position 7 Substituents

R2 is susceptible to hydrolysis. Substitution Influences Spectrum of Antibacterial Activity

ADR AND ALLERGIC AND CROSSALLERGIC REACTION risk factor

Their renal system is not working properly

Discovery of Thienamycin

Naturally occurring Carbapenem from the bacterium Streptomyces cattleya

Bicyclic Ring System: CARBAPENEM RING

Carbapanem is just a penicillin ring but sulfur was replaced with a carbon

Imipenem Role

Silastatin is not a beta lactamase inhibitor rather it is a dehydropeptidase inhibitor and Only used to enhanced kinetics

Spectrum of Activity: NARROW-SPECTRUM

Selective Against Aerobic Gram-Negative Bacilli

Monocyclic β-Lactam Ring

Negatively charged sulfonic acid (-SO₃H) group at C2

Vancomycin

Source: Streptomyces orientalis

Other Glycopeptides

They all act the same as Vancomycin, and Are Derivatives of Vancomycin

Autoclaving

A sterilization technique using high-pressure steam (121-134 °C) to kill microbes, including spores.

Ethylene Oxide Sterilization

A gaseous sterilization method effective against all microorganisms, including spores, but requires careful aeration due to toxicity.

HEPA Filtration

High-Efficiency Particulate Air filters that remove microorganisms and particles from the air in laboratory and healthcare settings.

Ionizing Radiation

Sterilization method using gamma or X-rays to damage microbial DNA, effective for heat-sensitive materials.

Plasma Sterilization

Uses ionized gas plasma to sterilize heat-sensitive and moisture-sensitive medical devices.

Peracetic Acid Sterilization

A liquid chemical sterilant used for heat-sensitive medical equipment, effective against a wide range of microorganisms.

Vaporized Hydrogen Peroxide (VHP)

A low-temperature sterilization process used for heat-sensitive medical devices and isolators.

Ozone Sterilization

Uses ozone gas to sterilize equipment and surfaces, effective against a broad spectrum of microorganisms.

Glutaraldehyde

A high-level disinfectant and sterilant used for medical equipment that cannot withstand heat sterilization.

Formaldehyde

Used as a disinfectant and sterilant in both liquid and gaseous forms, effective against bacteria, viruses, and fungi.

Quaternary Ammonium Compounds (Quats)

Cationic detergents used as disinfectants, effective against vegetative bacteria and enveloped viruses but less effective against spores.

Chlorhexidine

A broad-spectrum antiseptic used in healthcare settings for skin disinfection and wound care.

Triclosan

An antibacterial agent used in soaps, detergents, and other products, but its use has been restricted due to concerns about resistance and environmental impact.

Silver Nanoparticles

Used in medical devices and textiles for their antimicrobial properties.

Copper Alloys

Used for their inherent antimicrobial properties, effective against a range of bacteria, viruses, and fungi.

Probiotics

Live microorganisms that, when administered in adequate amounts, confer a health benefit on the host by modulating the gut microbiota.

Phage Therapy

Uses bacteriophages to target and kill specific bacteria, offering a potential alternative to antibiotics.

Antimicrobial Peptides (AMPs)

Small peptides with broad-spectrum antimicrobial activity, offering potential for new therapeutic agents.

Photodynamic Inactivation (PDI)

Uses photosensitizers and light to generate reactive oxygen species that kill microorganisms.

Essential Oils

Certain essential oils have antimicrobial properties and can be used as natural disinfectants.

Mechanism of Action: Beta-Lactams

Inhibit bacterial cell wall synthesis by binding to and inactivating penicillin-binding proteins (PBPs), preventing peptidoglycan cross-linking.

Resistance Mechanism: Beta-Lactamases

Enzymes produced by bacteria that hydrolyze the beta-lactam ring, rendering the antibiotic inactive.

Clavulanic Acid

A beta-lactamase inhibitor combined with beta-lactam antibiotics to protect them from degradation by bacterial enzymes.

Mode of Action: Glycopeptides

Inhibit bacterial cell wall synthesis by binding to the D-alanyl-D-alanine terminus of peptidoglycan precursors.

Resistance Mechanism: Vancomycin Resistance

Occurs when bacteria replace the D-alanyl-D-alanine terminus with D-alanyl-D-lactate, reducing vancomycin's binding affinity.

Classes of Penicillins

Include natural penicillins, aminopenicillins, carboxypenicillins, ureidopenicillins, and cephalosporins, each with varying spectra of activity and resistance to beta-lactamases.

Mode of Action: Quinolones

Inhibit bacterial DNA replication by targeting DNA gyrase and topoisomerase IV.

Resistance Mechanism: Fluoroquinolone Resistance

Develops through mutations in DNA gyrase and topoisomerase IV genes, as well as efflux pump overexpression.

Classes of Cephalosporins

Categorized into generations (1st to 5th) based on their spectrum of activity, with later generations generally having broader activity against Gram-negative bacteria.

Mode of Action: Aminoglycosides

Inhibit bacterial protein synthesis by binding to the 30S ribosomal subunit.

Antiseptics

Compounds that either kill (Cidal) or prevent growth (Static) of microorganisms when applied to living tissues.

Disinfection

Prevent the transmission of infection to inanimate objects

Decontamination

The combination of processes that removes or destroys contamination to prevent an infectious agent or contamination from reaching a susceptible site.