SYNTHESIS, CHARACTERIZATION, ANTIMICROBIAL ACTIVITIES OF QUINAZOLIN-4(3H)ONE SCAFFOLDS

Abstract

ABSTARCT The invention relates to quinazolinone-based compounds, a specialized class of heterocyclic organic molecules with azo and oxo-containing nuclei, recognized for diverse biological activities, including antimicrobial, antimalarial, antibacterial, antifungal, and anticancer properties. The compound synthesis begins with 2 aminobenzoic acid reacting with acid acyl chloride in the presence of dry pyridine to produce phenyl-2-benzoxazinone. This intermediate is further treated with substituted acetophenone, followed by cyclization with substituted aryl benzaldehydes, and finally reacts with an aromatic amine to yield the targeted quinazolinone derivative. The resultant compound was characterized using TLC, melting point, and spectroscopic methods, revealing notable antimicrobial efficacy. In antimicrobial assays, the compound demonstrated significant zones of inhibition, achieving maximum inhibition of 12 mm, 14 mm, and 24 mm against Bacillus subtilis, and 20 mm against Escherichia coli and Candida albicans. The enhanced biological properties of this synthesized quinazolinone derivative make it a valuable compound for further development in antimicrobial applications.

Specification

Description:FIELD OF INVENTION
The present invention relates to the field of This invention pertains to the field of
medicinal chemistry and organic synthesis, particularly the synthesis of
quinazolinone derivatives that exhibit antimicrobial properties.
BACKGROUND
Quinazolinone scaffolds are specialized type of azo and oxo-containing nucleus,
heterocyclic organic synthesis, that are well-known for their versatility. In which
forms various biological properties such as antimicrobials, antimalarial,
antibacterial, antifungal and anticancer activities etc.
Traditional antimicrobial agents have faced challenges with resistance, and there is
an ongoing need for novel compounds with effective antimicrobial action. This
invention addresses these needs by synthesizing a novel quinazolinone compound
that demonstrates promising antibacterial and antifungal activities.
Quinazolinone-based compounds have been widely studied for various biological
properties, with structures containing azo and oxo-functional groups being
particularly useful for their medicinal properties. However, existing quinazolinone
compounds in use as antimicrobials have been limited by resistance issues or
moderate activity levels. Traditional antimicrobial agents such as Ciprofloxacin and
Fluconazole are frequently employed but have noted resistance patterns. Hence,
there exists a demand for new quinazolinone derivatives with enhanced
antimicrobial efficacy.
OBJECTS OF THE INVENTION
The present invention has been developed in response to the present state of the art,
and in particular, in response to the problems and needs in the art that have not yet
been fully solved by currently available techniques and processes.
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Accordingly, the present invention has been developed to provide a synthesis,
characterization, antimicrobial activities of quinazolin-4(3H)-one scaffolds.
Therefore, the current invention successfully overcoming all of the above-discussed
shortcomings present in the art.
1.
It is an object of the invention to synthesize a novel quinazolinone scaffold
compound with antimicrobial properties.
2.
It is an object of the invention to provide a compound with enhanced
antimicrobial activity against specific bacterial strains (B. subtilis, E. coli) and
fungal strains (C. albicans).
3.
It is an object of the invention to characterize the synthesized compound
using TLC, melting point, IR-ATR, 1H-NMR, 13C-NMR, and HRMS.
4.
It is an object of the invention to pevaluate the antimicrobial activity of the
synthesized compound and compare it with standard antimicrobial agents.
How the foregoing objects are achieved will be clear from the following brief
description. In this context, it is clarified that the description provided is non
limiting and is only by way of explanation. Other objects and advantages of the
invention will become apparent as the foregoing description proceeds, taken
together with the accompanying drawings and the appended claims.
SUMMARY
This summary is provided to introduce a selection of concepts in a simplified
format that is further described in the detailed description of the invention. This
summary is neither intended to identify key or essential inventive concepts of the
invention and nor is it intended for determining the scope of the invention.
This invention relates to a novel quinazolinone-based compound featuring an azo
and oxo-containing nucleus, synthesized through a series of organic reactions
starting from 2-aminobenzoic acid. The compound exhibits substantial biological
activities, including antimicrobial, antibacterial, antifungal, antimalarial, and
anticancer properties. The synthesis involves forming an intermediate phenyl-2
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benzoxazinone, which undergoes further reactions with acetophenone, substituted
aryl benzaldehydes, and aromatic amine to yield the targeted quinazolinone.
The new compound, characterized by TLC, melting point, and spectroscopic
analysis (including IR, 1H NMR, and 13C NMR), shows a molecular formula of
C35H23ClFN3O2 and molecular weight of 537.58. Antimicrobial evaluation
conducted using the cup diffusion method against Bacillus subtilis, Escherichia
coli, and Candida albicans indicated notable inhibition zones, achieving maximum
inhibition of 12 mm, 14 mm, and 24 mm for B. subtilis and 20 mm for E. coli and
C. albicans.
This compound presents promising potential as a broad-spectrum antimicrobial
agent, offering an innovative option for treatments requiring antibacterial and
antifungal efficacy.
To further clarify the advantages and features of the present invention, a more
particular description of the invention will be rendered by reference to specific
embodiments thereof, which is illustrated in the appended figures. It is appreciated
that this figure depicts only typical embodiments of the invention and are therefore
not to be considered limiting of its scope. The invention will be described and
explained with additional specificity and detail with the accompanying figure.
BRIEF DESCRIPTION OF FIGURES
These and other features, aspects, and advantages of the present invention will
become better understood when the following detailed description is read with
reference to the accompanying figures in which like characters represent like parts
throughout the figures, wherein:
Figure 1, illustrates a view of a formula of 3-(4-(3-(4-(4-fluoro-phenylamino)
phenyl) acryloyl) phenyl)-2-phenylquinazolin-4(3H)-one for the present invention.
Further, skilled artisans will appreciate that elements in the figures are illustrated
for simplicity and may not have been necessarily been drawn to scale. For example,
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the flowcharts illustrate the method in terms of the most prominent steps involved
to help to improve understanding of aspects of the present invention. Furthermore,
in terms of the construction of the device, one or more components of the device
may have been represented in the figures by conventional symbols, and the figures
may show only those specific details that are pertinent to understanding the
embodiments of the present invention so as not to obscure the figures with details
that will be readily apparent to those of ordinary skill in the art having benefit of the
description herein.
DETAILED DESCRIPTION:
For the purpose of promoting an understanding of the principles of the invention,
reference will now be made to the embodiment illustrated in the figures and
specific language will be used to describe the same. It will nevertheless be
understood that no limitation of the scope of the invention is thereby intended, such
alterations and further modifications in the illustrated system, and such further
applications of the principles of the invention as illustrated therein being
contemplated as would normally occur to one skilled in the art to which the
invention relates.
It will be understood by those skilled in the art that the foregoing general
description and the following detailed description are exemplary and explanatory of
the invention and are not intended to be restrictive thereof.
Reference throughout this specification to "an aspect", "another aspect" or similar
language means that a particular feature, structure, or characteristic described in
connection with the embodiment is included in at least one embodiment of the
present invention. Thus, appearances of the phrase "in an embodiment", "in another
embodiment" and similar language throughout this specification may, but do not
necessarily, all refer to the same embodiment.
The terms "comprises", "comprising", or any other variations thereof, are intended
to cover a non-exclusive inclusion, such that a process or method that comprises a
list of steps does not include only those steps but may include other steps not
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expressly listed or inherent to such process or method. Similarly, one or more
devices or systems or elements or structures or components proceeded by
"comprises... a" does not, without more constraints, preclude the existence of other
devices or other systems or other elements or other structures or other components
or additional devices or additional systems or additional elements or additional
structures or additional components.
Unless otherwise defined, all technical and scientific terms used herein have the
same meaning as commonly understood by one of ordinary skill in the art to which
this invention belongs. The system, methods, and examples provided herein are
illustrative only and not intended to be limiting.
The terms "a" and "an" herein do not denote a limitation of quantity, but rather
denote the presence of at least one of the referenced items.
The terms "having", "comprising", "including", and variations thereof signify the
presence of a component.
Now the present invention will be described below in detail with reference to the
following embodiment.
Example 1:
Procedure of synthesis of 3-(4-(3-(4-(4-fluoro-phenylamino) phenyl) acryloyl)
phenyl)-2-phenylquinazolin-4(3H)-one
Weighed of 2-phenyl-3[4-(3- phenyl acryloyl)-phenyl]-3H-quinazolinone
(0.003mol) 1.39 gm and 4-fluoroaniline (0.003mol) 2.80 ml was dissolved in 40 ml
acetonitrile and added double mole of anhydrous potassium carbonate, in the
presence of few amounts of potassium iodide crystals. Then reaction solvent reflux
for 14-15 hours and the completion reaction check by TLC. After the reaction
mixture was filtered, the excess solvent removed by the vacuum distillation, cooled,
resulting product was washed and recrystallized by the solvents.
Example 2:
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Characterization:
Mole. formula C35H23ClFN3O2, Mole. weight 537.58, weight 0.68g, blackish
powder; 65.65%, mp. 135-38 0C, Rf; 0.75. IR-ATR (KBr) cm-1: 3409.43 N-H Str
(Ar), 3092.16 C-H Str (Ar), 2953.78 C-H Str (Al), 1705.44 & 1647.10 C=O Str,
1563.68 C=C Str, 1473.21 N-H Str Al, 1174.57 C-F Str Al. 1H NMR (500 MHz,
CDCl3) d ppm: 7.86-7.91 (4H, aromatic C-H), 7.71-7.82 (5H, aromatic C-H), 7.65
7.69 (4H, aromatic C-H), 7.47-7.54 (2H, aromatic C-H), 7.36-7.42 (4H, aromatic
C-H), 7.22-7.28 (3H, aromatic C-H), 2.92 (1H, aromatic N-H). 13CNMR (500 MHz,
CDCl3) d ppm: 187.7, 168.4, 166.8, 148.6, 146.7, 145.4, 142.9, 141.8, 140.7, 139.8,
139.4, 138.7, 136.4, 135.6, 134.5, 133.2, 132.1, 131.8, 131.2, 129.9, 129.1, 128.8,
128.3, 127.8, 124.4, 122.6, 122.2, 121.7, 121.2, 119.8, 115.6, 76.4, 75.9, 74.8, 29.6.
HRMS Calcd for m/z [M+H]+, 572.0316 (572.0410).
Example 3:
Evaluation of Antimicrobial activity:
The antimicrobial testing was performed using the cup diffusion technique. The
synthesized compound, as 1 mg/ml solutions in dimethyl sulfoxide (DMSO), was
evaluated in vitro for activity against B. Subtilis, E. Coli, C. albicans by the cup
diffusion technique. Ciprofloxacin and Fluconazole were used as standard
antimicrobial agents. Dimethyl sulfoxide was used as a control. Sterile nutrient agar
was inoculated with the test organisms (each 100 mL of the medium received 1 mL
of 48 h broth culture), and then seeded agar was poured into sterile petri dishes.
Cups (8 mm in diameter) were cut in the agar, and each cup received 0.1 mL of the
test compound solution. The plates were then incubated at 37 oC for 48 h. The
activities were estimated as zones of inhibition in mm diameter. Ciprofloxacin and
Fluconazole solutions (0.01%) were used as reference standards. DMSO did not
show any inhibition zones. The Synthesized compound was showed zone of
inhibition 12 mm, 14 mm, 24 mm against B. Subtilis, E. Coli, C. albicans
respectively as compare with standard drugs.
While the invention has been described with respect to specific composition which
include presently preferred modes of carrying out the invention, those skilled in the
art will appreciate that there are numerous variations and permutations of the above
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described embodiments that fall within the spirit and scope of the invention. It
should be understood that the invention is not limited in its application to the details
of construction and arrangements of the components set forth herein.
Variations and modifications of the foregoing are within the scope of the present
invention. Accordingly, many variations of these embodiments are envisaged
within the scope of the present invention.
The foregoing descriptions of specific embodiments of the present invention have
been presented for purposes of description. They are not intended to be exhaustive
or to limit the present invention to the precise forms disclosed, and obviously many
modifications and variations are possible in light of the above teaching.
The embodiments were chosen and described in order to best explain the principles
of the present invention and its practical application, and to thereby enable others
skilled in the art to best utilize the present invention and various embodiments with
various modifications as are suited to the particular use contemplated. It is
understood that various omissions and substitutions of equivalents are contemplated
as circumstances may suggest or render expedient, but such omissions and
substitutions are intended to cover the application or implementation without
departing from the spirit or scope of the present invention. , Claims:WE CLAIM:
1. A quinazolinone-based compound with the molecular formula C35H23ClFN3O2,
characterized by enhanced antimicrobial properties.
2. The quinazolinone-based compound as claimed in claim 1, wherein the
compound is designated as formula I.
O
O
N
N
Formula I
NH
F
3. The quinazolinone-based compound as claimed in claim 1, wherein the IUPAC
name of said compound is 3-(4-(3-(4-(4-fluoro-phenylamino) phenyl) acryloyl)
phenyl)-2-phenylquinazolin-4(3H)-one.
4. The quinazolinone-based compound as claimed in claim 1, synthesized from 2
phenyl-3[4-(3-phenyl acryloyl)-phenyl]-3H-quinazolinone and 4-fluoroaniline in a
molar ratio of 0.003 mol each, dissolved in acetonitrile and reacted with anhydrous
potassium carbonate and potassium iodide as a catalyst.
5. The quinazolinone-based compound as claimed in claim 1, wherein the synthesis
process involves dissolving the reactants in 40 ml of acetonitrile, adding a double
mole quantity of anhydrous potassium carbonate, and a small amount of potassium
iodide, followed by refluxing for 14-15 hours.
6. The quinazolinone-based compound as claimed in claim 1, wherein the
completion of the reaction is monitored by Thin Layer Chromatography (TLC).
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7. The quinazolinone-based compound as claimed in claim 1, wherein, upon
completion of the reaction, the reaction mixture is filtered, the solvent removed by
vacuum distillation, and the resulting product is cooled, washed, and recrystallized
to obtain a purified quinazolinone-based compound.
8. The quinazolinone-based compound as claimed in claim 1, wherein the resulting
product is a purified quinazolinone-based compound exhibiting antimicrobial
properties, suitable for further biological or pharmacological evaluation.
9. The quinazolinone-based compound as claimed in claim 1, evaluated using the
cup diffusion technique against bacterial strains B. subtilis, E. coli, and fungal
strain C. albicans.
10. The quinazolinone-based compound as claimed in claim 1, which shows a
maximum zone of inhibition of 12 mm, 14 mm, and 24 mm for B. subtilis, E. coli,
and C. albicans respectively.

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