Anti-Microbial Evaluation of Newly Synthesized Hetero-Aryl Thiazole Derivatives
Anima Biswas1, Divya Pujari2, Manisha Masih3, Arin Bhattacharya4
1Student, School of Pharmacy, Chouksey Engineering College, Bilaspur (CG) India.
2Student, J. K. College of Pharmacy, Near Gatora Railway Station, Bilaspur (CG) India.
3Assistant Professor, School of Pharmacy, Chouksey Engineering College, Bilaspur (CG) India.
4Associate Professor, HOD of Pharmacology, J. K. College of Pharmacy, Bilaspur (CG) India.
*Corresponding Author E-mail:
ABSTRACT:
Antimicrobial drugs have had a significant role in reducing the global burden of infectious diseases. Antimicrobial resistance (AMR) refers to the ability of organisms such as parasites, fungi, viruses, etc. among other microorganisms, to evolve and prosper in an environment full of medications1. Antibiotic overuse has led to the emergence of multidrug-resistant (MDR) microorganisms, culminating in higher mortality as well as disability rates. Methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococci (VRE), and MDR Gram-negative bacteria, specifically, cause several therapeutic drugs to lose potency or cease functioning entirely.
Furthermore, very invasive infections with fungi have presented a previously unknown obstacle to the healthcare industry.2-4 Antimicrobial drugs may be classified into various classes based on their mechanism of action. The key subdivisions include protein synthesis inhibiting agents, nucleic acid synthesis inhibiting agents, metabolic process inhibiting agents, including depolarizing compounds for cell membranes. Antibiotics are becoming less effective in treating infections caused by bacteria, signaling some unclear subsequent years for medical treatment. To tackle medicine tolerance in clinically significant illnesses, new compounds exhibiting antibacterial activity that may work via modes of action distinct from the ones found in well-known antimicrobial medication categories must be discovered. 6,7
Heterocyclic chemicals are carbocyclic molecules in which more than one ring atoms of carbon are swapped by the elements nitrogen, oxygen, sulfur, or another heteroatom. Heterocyclic chemicals have a wide range of biological action, making them useful as antibacterial, antiseptic, as well anti-inflammatory agents, and are also used in agricultural chemical substances along with animal health good8. The aforementioned have several uses in the field of materials research because to their biochemical iluminescence, photochromic, and solvatochromic capabilities. The components of DNA, RNA, plant green cholorphyll stuff, vitamins, hemoglobin, and enzymes are all composed of various heterocyclic molecules. Additionally, heterocycles may also be utilized as dyes, solvents, water-proofing agents, rubber additives, alcohol denaturants, and dyeing adjuncts. In synthesis organic chemistry, heterocycles are utilized as chiral subordinates, metal ligands, protective groups, organic catalysts, as well synthetic precursors. Heterocycles additionally have been used in inorganic synthesis9-11.
The ring of thiazole is acknowledged as an important heterocyclic architecture in the domains of organic as well medicinal chemistry, owing to its significance as the basic building block in a wide range of medicines. The aforementioned scaffold's strong pharmacological capabilities against a number of ailments have made it an ideal choice for commercial production. Recent research suggests that the number of medications integrating this ring is increasing, with a major high of 14 observed solely in 20234,12-14.
In accordance with the results that were presented above, the current study seeks to draw attention to significant advances in the anti-inflammatory, antimicrobial, along with cancer fighting properties of thiazole-containing chemicals, in addition trying to investigate the effect of several different alternates on this framework in relation to a diverse range of microorganisms including fungal strains.
All of the chemically produced substances listed in Scheme 1 were tested for antimicrobial properties employing the disc diffusion technique. Thiazole nucleus are used as components of numerous pharmaceutical products. They exhibit a wide range of biological actions, which can include antibacterial, antiviral, as anti-inflammatory activity as well anti-
HIV, anticancer, as well antioxidant effect. The effectiveness against different microbes from all samples were assessed towards a variety of gram positive along with gram negative pathogens using the method known as disc diffusion, described in the published work. The antimicrobial effectiveness was assessed using the disc diffusion technique at the Department of Pharmacy, CEC, Bilaspur, C.G.
Scheme 1: Synthesis of compounds 10a to 10ah with different functional group substitutions:
|
Compd. |
R2 (3rd C) |
R1 (4th C) |
R |
Compd. |
R2 (3rd C) |
R1 (4th C) |
R |
Compd. |
R2 (3rd C) |
R1 (4th C) |
R |
|
10aa |
|
H |
CH3 |
10ab |
|
Br |
CH3 |
10ac |
|
Cl |
CH3 |
|
10ad |
Cl |
F |
CH3 |
10ae |
|
F |
CH3 |
10af |
|
CH3 |
CH3 |
|
10ag |
|
CF3 |
CH3 |
10ah |
CH3 |
|
CH3 |
10a |
|
H |
H |
|
10b |
|
Br |
H |
10c |
|
Cl |
H |
10d |
Cl |
F |
H |
|
10e |
|
F |
H |
10f |
|
CH3 |
H |
10g |
|
CF3 |
H |
|
10h |
CH3 |
|
H |
10i |
|
H |
Br |
10j |
|
Br |
Br |
|
10k |
|
Cl |
Br |
10l |
Cl |
F |
Br |
10m |
|
F |
Br |
|
10n |
|
CH3 |
Br |
10o |
|
CF3 |
Br |
10p |
CH3 |
|
Br |
|
10q |
|
CF3 |
Cl |
10r |
CH3 |
|
Cl |
10s |
|
H |
F |
|
10t |
|
Br |
F |
10u |
|
Cl |
F |
10v |
Cl |
F |
F |
|
10w |
|
F |
F |
10x |
|
CH3 |
F |
10y |
|
CF3 |
F |
|
10z |
CH3 |
|
F |
|
|||||||
Table 2: Zone of inhibition in ‘millimeters’ of compounds 10a-ah
|
Mole. No. |
B. subtilis |
S. aureus |
E. coli |
Mole. No. |
B. subtilis |
S. aureus |
E. coli |
|
10b |
- |
- |
10 |
10s |
- |
22 |
10 |
|
10a |
- |
- |
13 |
10r |
16 |
14 |
24 |
|
10c |
- |
- |
14 |
10t |
- |
23 |
11 |
|
10e |
- |
- |
15 |
10v |
- |
25 |
- |
|
10d |
- |
- |
10 |
10u |
20 |
20 |
10 |
|
10f |
- |
07 |
15 |
10w |
- |
19 |
13 |
|
10h |
- |
- |
08 |
10y |
13 |
16 |
- |
|
10g |
- |
- |
14 |
10x |
- |
17 |
12 |
|
10i |
- |
- |
- |
10z |
- |
18 |
- |
|
10k |
- |
12 |
- |
10ab |
- |
- |
17 |
|
10j |
- |
- |
- |
10aa |
- |
25 |
20 |
|
10n |
12 |
12 |
08 |
10ae |
- |
- |
15 |
|
10l |
- |
- |
- |
10ac |
- |
- |
12 |
|
10p |
11 |
14 |
10 |
10ag |
- |
- |
12 |
|
10q |
- |
12 |
14 |
10ah |
- |
- |
13 |
|
10m |
10 |
11 |
10 |
10ad |
- |
- |
16 |
|
10o |
- |
- |
17 |
10af |
- |
19 |
20 |
|
Ciprofloxacin |
26 |
22 |
28 |
|
|
|
|
Here, blank (-) is for lack of anti-microbial outcomes.
All produced molecules were tested for antibacterial properties in vitro, contrary to the reference strains of Staphylococcus aureus (NCIM 2602), Escherichia coli (NCIM 2576), along with Bacillus subtilis (NCIM 2162). Each investigations were done at least twice.
The effectiveness against different bacterial strains, of abovementioned synthetic compounds was investigated through the disc diffusion technique. Tables 2 and 3 show biological activity data in terms of zone of inhibition measured in millimeters along with lowest inhibitory concentration, contrary to Escherichia coli (E.coli), Staphylococcus aureus (S. aureus), along with Pseudomonas aeruginosa (P. aeruginosa).
A thorough examination of the antimicrobial properties revealed several leading compounds exhibiting moderate to exceptional activity. The findings of antibacterial activity in vitro demonstrated that molecules 10r, 10aa, and 10af have good to exceptional microbiological effectiveness against E. coli. In a comparable manner compounds 10s, 10t, 10u, 10v, 10w, 10z, 10aa, and 10af had good to exceptional efficacy towards Staphylococcus aureus. The structure-activity connection demonstrated that substituents such as H, Br, Cl, F, CH3, along with CF3 substitution on phenyl at both the 2 or 2′ positions of the ring of thiazole had a substantial effect on the activity against bacteria. All of the analogues of 2-phenyl-4-(2′-substitutedphenylthiazol-4-yl) thiazole (10a-h) were shown to be not as effective against E. coli while these were inert towards S. aureus and B. subtilis strains. Amongst the compounds tested 2-(4-bromophenyl)-4-(2′-substituted phenylthiazol-4-yl) thiazole (10i-p), only molecule number 10o (R = Br, R1 = 4-CF3) had modest efficacy against the bacteria E. coli.
Table 3: Minimum Inhibitory Concentration in ‘µM’ of compounds 10a-ah
|
Mole. No. |
B. subtilis |
S. aureus |
E. coli |
Mole. No. |
B. Subtilis |
S. aureus |
E. coli |
|
10c |
- |
- |
250 |
10t |
- |
15.6 |
1000 |
|
10a |
- |
- |
500 |
10r |
125 |
250 |
7.8 |
|
10d |
- |
- |
1000 |
10u |
31.3 |
31.3 |
1000 |
|
10b |
- |
- |
1000 |
10s |
- |
15.6 |
1000 |
|
10e |
- |
- |
250 |
10v |
- |
7.8 |
- |
|
10g |
- |
- |
250 |
10x |
- |
125 |
500 |
|
10f |
- |
1000 |
250 |
10w |
- |
62.5 |
500 |
|
10k |
- |
500 |
- |
10ab |
- |
- |
125 |
|
10h |
- |
- |
1000 |
10y |
500 |
125 |
- |
|
10l |
- |
- |
- |
10ac |
- |
- |
500 |
|
10i |
- |
- |
- |
10z |
- |
62.5 |
- |
|
10n |
500 |
500 |
1000 |
10ae |
- |
- |
250 |
|
10j |
- |
- |
- |
10aa |
- |
7.8 |
31.3 |
|
10p |
1000 |
250 |
1000 |
10ag |
- |
- |
500 |
|
10q |
- |
500 |
250 |
10ah |
- |
- |
500 |
|
10m |
1000 |
1000 |
1000 |
10ad |
- |
- |
125 |
|
10o |
- |
- |
125 |
10af |
- |
62.5 |
31.3 |
|
Ciprofloxacin |
7.8 |
62.4 |
15.6 |
|
|
|
|
Here, blank (-) is for lack of anti-microbial outcomes.
Compound 10r (R = Cl, R1 = 3-CH3) demonstrated good efficacy against E. coli having MIC value of 7.8 μM, twice greater than the conventional medication.
Each of the variants of 2-(4-fluorophenyl)-4-(2′-substitutedphenylthiazol-4-yl) thiazole (10s-z) appeared to be less successful towards E. coli, but all exhibited moderate to exceptional effectiveness towards Staphylococcus aureus with MIC value ranging from 7.8 to 125 micromole. Molecule number 10s (R = F, R1 = H) demonstrated fourfold higher action towards S. aureus than the conventional medication. This efficacy was maintained when 2′-phenylthiazol-4-yl was replaced with 2′-(4-bromophenyl) thiazol-4-yl in molecule 10t (R = F, R1 = 4-Br).
Compound 10u (R = F, R1 = 4-Cl) shown double effectiveness towards S. aureus, whereas compounds 10w (R = F, R1 = 4-F) and 10z (R = F, R1 = 3-CH3) had equivalent activity. Compound 4-(2′-(4-chloro- 3-fluorophenyl) thiazol-4-yl)-2-(4-fluorophenyl) thiazole 10v (R = F, R1 = 3-Cl,4-F) shown outstanding efficacy with MIC 7.8 micro molar, eight times higher compared to the conventional medication. Molecules number 10x (R = F, R1 = 4-CH3) along with 10y (R = F, R1 = 4-CF3) were shown to be twice less effective towards Staphylococcus aureus. Molecule number 10u (R = F, R1 = 4-Cl) was however, found to be effective towards the Bacillus subtilis species, with a MIC value of 31.3 micro molar, while the remainder of the molecules were observed to be ineffective.
Molecules number10ab (R = CH3, R1 = 4-Br) along with 10ad (R = CH3, R1 = 4-F) demonstrated minimal effectiveness towards Escherichia coli species, while molecules 10aa (R = CH3, R1 = H) along with 10af (R =CH3, R1 = CH3) demonstrated significant effectiveness having MIC value of 31.3 micro molar, a concentration nearly less by a factor of two, comparison to the standard the medication. Molecule number 10aa (R = CH3, R1 = H) shown outstanding action against Staphylococcus aureus having MIC value 7.8 micro molar, eight times more than that of the conventional medication, whereas molecule number 10af (R = CH3, R1 = CH3) demonstrated similar effectiveness. It was discovered that compounds 10aa-ah had no effect on Bacillus subtilis species.
It is noteworthy from SAR study, that the action against Staphylococcus aureus required 4-fluorophenyl at the 2-position of thiazole, as in molecule 2-(4-fluorophenyl)-4-(2′-substitutedphenylthiazol-4-yl) thiazole, (10s-z).
Substantial antibacterial efficacy towards gram-positive bacteria as well gram-negative bacteria along with fungal pathogens has been shown by some thiazole compounds15,16. The current study's findings were comparable to those of Sayed et al. for their synthesised molecule number 12, which showed the most significant MIC value for Bacillus pumillis of 7.69 micro mole per milliliter 5.
To sum up, a number of novel substituted 2,2'-diaryl-4,4'-bisthiazole analogues (10a-ah) have been created and tested for their ability to inhibit microorganisms. Based on the findings generated by biological assessment, 2-(4-chlorophenyl) towards E. coli, -4-(2-m- tolylthiazol-4-yl) thiazole, (10r) had outstanding activity. 2-(4-fluorophenyl)4-(2-(4-bromophenyl) thiazol-4-yl), 4-(2-(4-phenylthiazol-4-yl)thiazole (10s)5-(2-(4-chlorophenyl)thiazol-4-yl), 2-(4-fluorophenyl)thiazole (10t) (2)4-(2-(4-chloro-3-fluorophenyl)thiazol-4-yl), 4-(2-(4-fluorophenyl)thiazole (10u)10-av, 2-(4-fluorophenyl)thiazole, 2-(4-fluorophenyl)The compound 2-(4-fluorophenyl)thiazol-4-yl)thiazole (10w), 2-(4-fluorophenyl)4-(2-phenylthiazol-4-yl), 4-(2-m-tolylthiazol-4-yl)thiazole (10z) having MICs value ranging from 7.8 to 62.5 micro molar. 2-p-tolyl-4-(2-p-tolylthiazol-4- yl) thiazole (10af) along with -2-p-tolylthiazole (10aa) demonstrated good to exceptional effectiveness towards Staphylococcus aureus. Having a MIC of 31.3 micro molar towards Bacillus subtilis, the molecule 4-(2-(4-chlorophenyl) thiazol-4-yl)-2-(4-fluorophenyl) thiazole (10u) proved to have maximum efficacy among the compounds evaluated. Investigations have shown that thiazole compounds have exceptional pharmacological efficacy.
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Received on 28.04.2025 Revised on 21.05.2025 Accepted on 07.06.2025 Published on 12.08.2025 Available online from August 18, 2025 Asian J. Research Chem.2025; 18(4):246-250. DOI: 10.52711/0974-4150.2025.00038 ©A and V Publications All Right Reserved
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