Developments of antifungal agents have declined as compared to other antibiotics that have displayed a potent development with time. There is an urgent need for both prophylactic and therapeutic treatments worldwide to control the severity of infections caused by Candida. Anticandidal Therapeutics: Discovery and Development provides the readers with a compiled knowledge of the fungal human infection Candida and the development of anticandidal drugs. Anticandidal Therapeutics helps researchers form the basis for the discovery and development of novel anticandidal therapies. In 14 chapters this book provides collective information on anticandidal agents and their discovery and development with respect to major drug transporter families, different stages of anticandidal agent development, recent trends and progress in antifungal translational research, clinical studies status of anticandidal therapeutic agents, and drug repurposing for development of novel anticandidal agents.
Author(s): Awanish Kumar, Anubhuti Jha
Series: Developments in Microbiology
Publisher: Academic Press
Year: 2023
Language: English
Pages: 181
City: London
Anticandidal TherapeuticsDiscovery and DevelopmentAwanish KumarAssociate Professor, Department of Biotechnology, National I ...
Copyright
Dedication
Preface
Acknowledgments
1. History of infection
Introduction
Introduction to plague
Types of plague
14th century plagues
Plague of Athens
Second plague pandemic
Black Death
Third plague pandemic
Smallpox
Tuberculosis
Spanish flu
HIV/AIDS
Swine flu
COVID-19 (current pandemic)
A note on the future
References
2. Brief introduction on infection
Introduction
References
3. Fungal diseases and antifungal drugs
Introduction
Superficial mycoses
Cutaneous mycoses
Subcutaneous mycoses
Systemic or invasive mycoses
Candidal infection
Biofilm formation
Adhesion and invasins
Contact sensing and thigmotropism
Hydrolytic enzymes
pH sensing and regulation
Metabolic adaptation
Environmental stress response
Heat shock protein
Metal acquisition
Antifungal agents
Azoles
Polyenes
Echinocandins
Allylamines
Other drugs
Mechanism of antifungal resistance
Resistance to azoles
Alteration of drug target
Upregulation of multidrug transporters
Cellular stress responses
Biofilms
Modification of ergosterol biosynthetic pathway
Chromosomal alterations
Resistance to polyenes
Resistance to echinocandins
Upregulation of multidrug transporters
Drug efflux
References
4. Multidrug transporters of fungal pathogen Candida
Introduction
ABC transporters
MFS transporters
Regulation of MDR
PDR1 and PDR3 are xenobiotic receptor in S. cerevisiae
Xenobiotic regulation
Efflux pumps regulation
References
5. Essential anticandidal targets
Fungal cell wall
Fungal membrane components
Inhibition of heat shock protein 90
Inhibition of calcineurin signaling
Signaling pathways
Cell cycle control pathways
Membrane transporters
Other surface targets
Cross-talk
References
6. Stages of anticandidal agent development
Introduction
Drug target discovery
Screening
HIT identification
Lead optimization
Experimentation
Characterization of product
Formulation, delivery, packaging development
Pharmacokinetics and drug disposition
Preclinical testing and IND application
Acute studies
Repeated dose studies
Generic toxicity studies
Reproductive toxicity studies
Carcinogenicity studies
Toxicokinetic studies
Bioanalytical testing
Clinical trials
Postmarketing surveillance
References
7. Recent trends and progress in antifungal translational research
Introduction
Translational research and strategy in fungal infection
References
8. Clinical status of anticandidal therapeutic agents
Introduction
Synthetic compounds as futuristic antifungal
Olorofim: orotomides (F901318)
Natural compounds as promising antifungal
Curcumin
Thymol
Berberine
Tetrandrine
Antifungals in different stage of clinical trials
Rezafungin
Ibrexafungerp (SCY-078)
Fosmanogepix (APX001)
Nikkomycin Z
Tetrazoles
Encochleated amphotericin B (MAT2203)
Aureobasidin A
F901318 (olorofim)
VL-2397
T-2307
AR-12
References
9. Drug repurposing for development of effective anticandidals
Introduction
References
10. Commercial aspects of drug development
Introduction
Drug development process
The design of a clinical trial
Different types of clinical research
Informed consent
The investigational new drug process
Drug review
New drug application
Postmarketing drug safety monitoring
Generic drugs
Reasons for catastrophic marketing failures
Failures of pharmaceutical companies
References
11. Challenges and future prospects
Introduction
Gray areas in drug discovery research
Cost of new drug development
Out-of-pocket costs
Success rates
Development timelines
Cost of capital
Preclinical phase
Clinical trials phase
Macroeconomic, demographic, and policy factors affecting R&D funding
References
Index
A
B
C
D
E
F
G
H
I
L
M
N
O
P
Q
R
S
T
U
V
W
X
