Bioorganic & Medicinal Chemistry Letters 16 (2006) 4571–4574
Synthesis and evaluation of phenoxy acetic acid derivatives
as a anti-mycobacterial agents
Mohammad Shahar yar,* Anees Ahmad Siddiqui and Mohamed Ashraf Ali
Faculty of Pharmacy, Jamia Hamdard University, Department of Pharmaceutical Chemistry, Hamdard Nagar,
New Delhi 110062, India
Received 22 February 2006; revised 16 May 2006; accepted 6 June 2006
Available online 19 June 2006
Abstract—In present investigation, 2-(4-formyl-2-methoxyphenoxy) acetic acid on condensation with various ketones in methanolic
KOH solution yielded the corresponding chalcones (1–3). These corresponding chalcones were reacted with appropriate acid hydra-
zide in glacial acetic acid led to the formation of phenoxy acetic acid derivatives. All newly synthesized compounds were evaluated
for their anti-mycobacterial activities against Mycobacterium tuberculosis H37Rv.
Ó 2006 Elsevier Ltd. All rights reserved.
Tuberculosis is by far the most frequently encountered
mycobacterial disease in the world. Among infectious
diseases, tuberculosis (TB) is the number one killer
with over two million casualties annually worldwide.
The WHO considers tuberculosis, to be the most dan-
gerous chronic communicable disease in the world.
The emergence of AIDS, decline of socioeconomic
standards and a reduced emphasis on tuberculosis
control programs contribute to the disease’s resurgence
in industrialized countries. Resistance of Mycobacteri-
um tuberculosis strains to anti-mycobacterial agents is
an increasing problem worldwide. However, powerful
new anti-TB drugs with new mechanism of action
have not been developed in the last forty years. In
spite of severe toxicity on repeated dosing of isoniazid
(INH), it still considered to be a first line drug for
chemotherapy of tuberculosis. Literature survey
reveals pyrazoline derivative possess the various
The synthesis of pyrazoline derivatives has been
carried out following the steps shown in schemes. In
the initial step, chalcones (1–3) were synthesized by
condensing 2-(4-formyl-2-methoxyphenoxy) acetic acid
with various ketones in dilute methanolic potassium
hydroxide solution at room temperature by Claisen–
Schimidt condensation. The compounds (4–24) were
synthesized by reacting chalcones with appropriate
aryl acidhydrazides in glacial acetic acid at 4 h. The
purity of the compounds was checked by single spot
TLC method using various mobile bases; Spectral data
1
(IR, H NMR, 13C NMR, and Mass). Both analytical
and spectral data of all the newly synthesized
compounds were in full agreement with purposed
structures (Table 1).
Twenty compounds were screened for their anti-myco-
bacterial activity against M. tuberculosis H37 Rv using
BACTEC-460 radiometric system8,9 and INH resistant
M. tuberculosis (INHR-MTB) using agar dilution
method.10 Among the chalcones (1–3) and pyrazolines
(4–24). Compounds 7 and 10 produced highest efficacy
and exhibited >99% inhibition at ꢀ6.25 lg/ml.
Compounds 14 exhibited ꢀ95 % inhibition against
M. tuberculosis at MIC ꢀ6.25 lg/ml in the primary
screen Table 2. The MIC was defined as the minimum
concentration of compound required to inhibit 90% of
bacterial growth and MICs of the compounds were
reported in Table 2 with standard drug INH for
comparison. Among the twenty newly synthesized
compounds three compounds were found to be
most active compounds with minimum inhibitory
biological activities viz. anti-bacterial and anti-fungal,1
3
anti-diabetic,2 anti-inflammatory
and also active
against many Mycobacterias.4–7 The current work
describes the synthesis of novel pyrazoline moiety with
encouraging
anti-mycobacterial
activity
against
M. tuberculosis H37Rv and INH resistant M. tubercu-
losis (INHR-MTB) (Scheme 1).
Keywords:
tuberculosis.
Pyrazoline;
Anti-mycobacterial;
Mycobacterium
*
Corresponding author. Tel.: +91 9899452373; fax: +91 11
0960-894X/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.bmcl.2006.06.021
yar, Mohammad Shahar
