Syed Nasir Abbas Bukhari(Old student Faculty of Pharmacy, University of Sargodha. 1st Ph.D degree holder),*, Scott G. Franzblau2, Ibrahim Jantan1 and Malina Jasamai1
1Drug and Herbal Research Center, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Kuala Lumpur, 50300,
Malaysia; 2Institute for Tuberculosis Research, College of Pharmacy, University of Illinois at Chicago, Chicago, IL
60612-7231, USA
treatment regimen, the difficulty in eradicating the infection in immune-suppressed patients, and multidrug resistance
(MDR). Extensive research circumscribing molecules to counteract this disease has led to the identification of many inhibitory
small molecules. Among these are chalcone derivatives along with curcumin analogs. In this review article, we
summarize the reported literature regarding anti tubercular activity of chalcone derivatives and synthetic curcumin analogs.
Our goal is to provide an analysis of research to date in order to facilitate the synthesis of superior antitubercular
chalcone derivatives and curcumin analogs.
Keywords: Chalcones, Anti-Tubercular, Mycobacterium tuberculosis, Curcumin.
INTRODUCTION:
Infectious diseases are leading causes of morbidity and
mortality worldwide. Tuberculosis, caused by Mycobacterium
tuberculosis (M. tb), is one of the principal infectious
diseases [1, 2]. Tuberculosis (TB) is by far the most prevalent
mycobacterial disease in the world and the only one having
a high mortality rate. Even the prevalence of TB has
lessened considerably in the developed countries; it still remains
a major public health problem in the developing nations.
Annually, more than 9 million TB cases are diagnosed,
resulting in almost 2 million deaths globally [3].
Mycobacteria are ubiquitous organisms that are becoming
increasingly important intracellular pathogens responsible
for establishing an infection in the oxygen-rich macrophage
of the lung [4]. The emergence of AIDS, decline of
socioeconomic standards and a reduced emphasis on tuberculosis
control programs contribute to the disease’s resurgence
in developed countries [5]. Resistance of M. Tuberculosis
strains to anti-mycobacterial agents is a universal problem
[6]. In some cases, in spite of toxicity on repeated dosing
of isoniazid (INH), it is still considered to be the first line
of therapy for tuberculosis [7].
The annual infection rate in the developing countries is
20-50 times greater than the developed countries and its peak
level shows little or no downward trend. Experts believe that
the development of new, effective anti-TB drugs will
achieve the desired goals by reducing the duration of therapy,
decreasing the total expenditure and treating multiple
drug resistant tuberculosis (MDR-TB) through a single dosage
regimen [8, 9].
Treatment of tuberculosis is a difficult task because of
various factors which include patient’s non-compliance and
MDR (multidrug resistance) [10-12]. Antibiotics are being
used to treat this infection, but this pathogenic species is
becoming resistant. Since the resistance increases day by
day, there is a need for designing novel antibiotics.
Chalcones, one of the main classes of natural products,
with widespread distribution in fruits, vegetables, spices, tea
and soya based foodstuffs, are of great interest due to their
pharmacological activities [13]. Chalcones or 1,3-diaryl-2-
propen-1-ones belong to the flavonoid family [14, 15]. From
the structural perspective, they consist of open-chain flavonoids
in which two aromatic rings are joined by a threecarbon
!,"-unsaturated carbonyl unit (Fig. 1).
Fascinatingly, a number of naturally occurring chalcones
are polyhydroxylated on both aryl rings, conferring them
noteworthy radical-quenching properties which have raised
interest in using chalcones or chalcone-rich plant extracts as
drugs or food preservatives [16]. In addition, chalcones have
been reported to possess many useful biological activities
including anti-inflammatory, antimicrobial, antifungal, antioxidant,
cytotoxic, antitumor and anticancer activities [14,
16, 17].
Curcumin (1,7-bis-(4-hydroxy-3-methoxyphenyl)-1, 6-
heptadiene-3, 5-dione) has achieved most attention among
all the species of Curcuma. Curcumin is renowned for its
various biological and pharmacological activities [18, 19].
Curcumin has been known to restrain the metabolism of arachidonic
acid and the activities of cyclooxygenase-2 (COX-
2), lipoxygenase, proinflammatory cytokines, inducible nitric
oxide (iNOS), protein kinases, transcription factors (including
nuclear factor-kB) and release of steroids [20-22]. Added
activities of curcumin include inhibition of low-density lipoprotein
oxidation, lowering of blood cholesterol level, inhibi
*Address correspondenc to this author at the Faculty of Pharmacy, Universiti
Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, 50300, Kuala
Lumpur, Malaysia; Tel: 0060142765730; Email: snab_hussaini@yahoo.com
1Drug and Herbal Research Center, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Kuala Lumpur, 50300,
Malaysia; 2Institute for Tuberculosis Research, College of Pharmacy, University of Illinois at Chicago, Chicago, IL
60612-7231, USA
Abstract: Tuberculosis, caused by Mycobacterium tuberculosis, is amongst the foremost infectious diseases. Treatment
of tuberculosis is a complex process due to various factors including a patient’s inability to persevere with a combinedtreatment regimen, the difficulty in eradicating the infection in immune-suppressed patients, and multidrug resistance
(MDR). Extensive research circumscribing molecules to counteract this disease has led to the identification of many inhibitory
small molecules. Among these are chalcone derivatives along with curcumin analogs. In this review article, we
summarize the reported literature regarding anti tubercular activity of chalcone derivatives and synthetic curcumin analogs.
Our goal is to provide an analysis of research to date in order to facilitate the synthesis of superior antitubercular
chalcone derivatives and curcumin analogs.
Keywords: Chalcones, Anti-Tubercular, Mycobacterium tuberculosis, Curcumin.
INTRODUCTION:
Infectious diseases are leading causes of morbidity and
mortality worldwide. Tuberculosis, caused by Mycobacterium
tuberculosis (M. tb), is one of the principal infectious
diseases [1, 2]. Tuberculosis (TB) is by far the most prevalent
mycobacterial disease in the world and the only one having
a high mortality rate. Even the prevalence of TB has
lessened considerably in the developed countries; it still remains
a major public health problem in the developing nations.
Annually, more than 9 million TB cases are diagnosed,
resulting in almost 2 million deaths globally [3].
Mycobacteria are ubiquitous organisms that are becoming
increasingly important intracellular pathogens responsible
for establishing an infection in the oxygen-rich macrophage
of the lung [4]. The emergence of AIDS, decline of
socioeconomic standards and a reduced emphasis on tuberculosis
control programs contribute to the disease’s resurgence
in developed countries [5]. Resistance of M. Tuberculosis
strains to anti-mycobacterial agents is a universal problem
[6]. In some cases, in spite of toxicity on repeated dosing
of isoniazid (INH), it is still considered to be the first line
of therapy for tuberculosis [7].
The annual infection rate in the developing countries is
20-50 times greater than the developed countries and its peak
level shows little or no downward trend. Experts believe that
the development of new, effective anti-TB drugs will
achieve the desired goals by reducing the duration of therapy,
decreasing the total expenditure and treating multiple
drug resistant tuberculosis (MDR-TB) through a single dosage
regimen [8, 9].
Treatment of tuberculosis is a difficult task because of
various factors which include patient’s non-compliance and
MDR (multidrug resistance) [10-12]. Antibiotics are being
used to treat this infection, but this pathogenic species is
becoming resistant. Since the resistance increases day by
day, there is a need for designing novel antibiotics.
Chalcones, one of the main classes of natural products,
with widespread distribution in fruits, vegetables, spices, tea
and soya based foodstuffs, are of great interest due to their
pharmacological activities [13]. Chalcones or 1,3-diaryl-2-
propen-1-ones belong to the flavonoid family [14, 15]. From
the structural perspective, they consist of open-chain flavonoids
in which two aromatic rings are joined by a threecarbon
!,"-unsaturated carbonyl unit (Fig. 1).
Fascinatingly, a number of naturally occurring chalcones
are polyhydroxylated on both aryl rings, conferring them
noteworthy radical-quenching properties which have raised
interest in using chalcones or chalcone-rich plant extracts as
drugs or food preservatives [16]. In addition, chalcones have
been reported to possess many useful biological activities
including anti-inflammatory, antimicrobial, antifungal, antioxidant,
cytotoxic, antitumor and anticancer activities [14,
16, 17].
Curcumin (1,7-bis-(4-hydroxy-3-methoxyphenyl)-1, 6-
heptadiene-3, 5-dione) has achieved most attention among
all the species of Curcuma. Curcumin is renowned for its
various biological and pharmacological activities [18, 19].
Curcumin has been known to restrain the metabolism of arachidonic
acid and the activities of cyclooxygenase-2 (COX-
2), lipoxygenase, proinflammatory cytokines, inducible nitric
oxide (iNOS), protein kinases, transcription factors (including
nuclear factor-kB) and release of steroids [20-22]. Added
activities of curcumin include inhibition of low-density lipoprotein
oxidation, lowering of blood cholesterol level, inhibi
*Address correspondenc to this author at the Faculty of Pharmacy, Universiti
Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, 50300, Kuala
Lumpur, Malaysia; Tel: 0060142765730; Email: snab_hussaini@yahoo.com
