ANTI-TUBERCULAR AGENTS AND

NEW TARGETS
Anho-nath Jesukparobo Daniel
21810874

Supervisor : Ayla Balkan

CYPRUS INTERNATIONAL UNIVERSITY

Major: PHARMACY
Talents come from diligence, and knowledge is
gained by accumulation.
 OUTLINE
01 Introduction; Tuberculosis, past
and present
02 Mode of transmission, causes and symptoms

Anti-tubercular drugs; first and

03
second line
04 New targets for Anti-tubercular Agents

05 Conclusion

06 References
 03

Introduction; Tuberculosis, past and

present

Tuberculosis (TB) is an airborne disease caused by mycobacteria.

It usually affects the lungs leading to severe coughing, fever, and chest
pains.It usually affects the lungs leading to severe coughing, fever, and
chest pains.
 04
Introduction; Tuberculosis, past and
present

 In the past treatment consisted of rest in the open air in

specialized sanatoria.
 The development of roentgenology - 1920-30
 In 1946 discovery that streptomycin was effective against
the disease.
 in 1952 isoniazid became available, most patients were
able to be cured of tuberculosis.
 In 1970, rifampin, an even more effective drug, was
approved.
 05
Introduction; Tuberculosis, past and
present
Baguley Chest Clinic (Wythenshawe It was thought that the clean air of countrified
Baguley would act as a tonic to sufferers from
Hospital) Sanitorium the smokey city of Manchester.
 06
introduction contd; Brief overview of tuberculosis as a
global health concern

• By the end of 2015, 10.4

million people worldwide
were caught in this disease.
Tuberculosis, used to be
considered only as a
disease of underdeveloped
countries and people living
in poverty.
 07
Mode of transmission, causes and
symptoms
• Transmission occurs by
inhalation of airborne droplet
nuclei that can be viable for
days, and is facilitated by
substance abuse, poverty,
overcrowding, malnutrition,
and, most importantly
coinfection with human
immunodeficiency virus.
 08
Mode of transmission, causes and symptoms
The symptoms may vary depending on what type of
tuberculosis you contract.
• Tuberculosis may be expelled
when an infectious person:
• Coughs
• Sneezes
• Speaks
• Sings
• laughs
09 Mode of transmission, causes and symptoms

Schematic representation of the life cycle of M. tuberculosis


Anti-tubercular drugs
• Anti-tubercular agents are
medications used to treat
tuberculosis and inhibit the
growth of mycobacteria.
• They can be categorized into
first-line and second-line
drugs, depending on their
primary usage and efficacy.
10
• First-Line Anti-Tubercular Agents:
• First-line drugs are the primary medications
used in standard TB treatment.
• Each drug targets specific mechanisms
involved in inhibiting the growth and
reproduction of mycobacteria.
• Second-Line Anti-Tubercular Agents:
• Second-line drugs are used when TB
strains show resistance to first-line
medications.
• They include drugs like streptomycin,
fluoroquinolones, These drugs have
different targets and mechanisms of action
compared to first-line agents.
 11
Anti-tubercular drugs
 12
Anti-tubercular drugs; first line

Rifampin ENTER TITLE

STRUCTURE OF RIFAMPIN
The user can perform
• Chemical formula of the presentation on a

Rifampin C43H58N4O12. projector or computer

The user can perform

the presentation on a
projector or computer
 13

Anti-tubercular drugs; first line

Mechanism of Action;
Rifampin produces bactericidal antimicrobial activity by inhibiting DNA-
dependent RNA polymerase (RNAP) either by sterically blocking the path of
the elongating RNA at the 5' end or by decreasing the affinity of the RNAP
for short RNA transcripts. It specifically inhibits the microbial RNAP,
halting further RNA synthesis.

Synthesis;
Rifamycin B is obtained from the fermentation liquid of Streptomyces
mediterranei (Amycolatopsis rifamycinica).
Rifampicin is then obtained by synthetically modifying Rifamycin B.
 14
Anti-tubercular drugs; first line
 15
Anti-tubercular drugs; first line cont’d

BRANDS
• ISONIAZID •NYDRAZIDE
• Isoniazid was first made in (Wilshire)
• ISONIAZID
the early 20th century. (Unexo)
• FAIRZIDE
• It is on the World Health (Ferro)
Organization's List of
Essential Medicines, a list
of medicines that constitute
the bare minimum for a
basic health system.
 16
Anti-tubercular drugs first line cont’d

• MECHANISM OF ACTION synthesis

• - Inhibits synthesis of
mycolic acid which is an
essential components of
mycobacterial cell wall
• • Isoniazid is a prodrug that is
activated by KatG, the
mycobacterial catalase-
peroxidase.
• • Isoniazid has bactericidal
effect.
 17
Anti-tubercular drugs; second line cont’d
 18

New targets for Anti-tubercular Agents

A new antitubercular drug should fulfill the following criteria:

(a) should have a validated safety profile;

(b) should result in shorter, safer, cheaper, and more effective
treatment alternatives for MDR-TB;
(c) should be effective on newer targets so as to circumvent MDR-TB
and XDR-TB;
(d) must be compatible with antiretroviral therapy, for the treatment of
a large population of HIV-TB coinfected patients;
(e) should not result in drug interactions with other anti-TB drugs or
drug candidates.
 20

New targets for Anti-tubercular Agents

Researchers are exploring new drugs
and targets to develop more effective
anti-tubercular agents.

Bedaquiline and delamanid are the

recently approved two new anti-TB drugs

Structure of Bedaquiline
 19

• Bedaquiline was approved in 2012 for use in treatment of MDR-TB by the

Food and Drug Administration (FDA).The ability of bedaquiline to be
bactericidal for both replicating as well as dormant bacteria could also
shorten the prolonged TB treatment.
• Adenosine triphosphate synthase is one such recently discovered target of
the newly approved antitubercular drug bedaquiline.

• Cytochrome bcc is another new target of the antitubercular drug candidate

Q203, currently in phase II clinical trial. Research suggests that b subunit of
cytochrome bcc, QcrB, is the target of Q203

• shikimate pathway and its key enzyme, shikimate kinase (SK).

Understanding the interactions between SK and its substrates opens up
possibilities for the development of new antitubercular drugs.
 21
Conclusion
In conclusion, the fight against tuberculosis (TB) continues to be a global health
challenge. While significant progress has been made in the development of
antitubercular agents, there is still much to be done to effectively reduce TB
incidence and ultimately eradicate the disease.

One potential avenue for future research lies in the shikimate pathway and its key
enzyme, shikimate kinase (SK). Understanding the interactions between SK and
its substrates opens up possibilities for the development of new antitubercular
drugs. and also bedaquiline targets the ATP synthase ;energy metabolism of
mycobacteria

Collaboration between researchers, pharmaceutical companies, and governments

is crucial for advancing anti-tubercular drug development.
 22

References

 Aparna Bahuguna, Srishti Rawat, Diwan S. Rawat.QcrB in Mycobacterium tuberculosis: The new drug target of
antitubercular agents.2021

 David E. Griffith, Md Clark M. Kerr, Md. Tuberculosis: Disease of the Past, Disease of the Present. .Science
direct.10.1016/S1089-9472(96)80023-2

 Inderbir S. Padda; Kona Muralidhara Reddy. Antitubercular Medications

 Pereira, Jose H.; Vasconcelos, Igor B.; Oliveira, Jaim S.; Caceres, Rafael A.; de Azevedo, Walter F.; Basso, Luis A.;
Santos, Diogenes S. Shikimate Kinase: A Potential Target for Development of Novel Antitubercular Agents
Current Drug Targets, Volume 8, Number 3, 2007, pp. 459-468(10)
THANK YOU
Tutor: Ayla Balkan

Talents come from diligence, and knowledge is

gained by accumulation.