|
||||||||||||||||
| Synthesis of Bioactive Fluorinated 2-Aminobenzenethiols and their Biological Activity | ||||||||||||||||
| Paper Id :
17784 Submission Date :
01/06/2023 Acceptance Date :
07/06/2023 Publication Date :
10/06/2023
This is an open-access research paper/article distributed under the terms of the Creative Commons Attribution 4.0 International, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. For verification of this paper, please visit on
http://www.socialresearchfoundation.com/remarking.php#8
|
||||||||||||||||
| ||||||||||||||||
| Abstract | Heterocyclic Chemistry is a thrust area for Chemists. Biologically active substituted benzenethiols in recent years have aroused our interest in the synthesis and biological activity of these heterocycles. This article reports synthesis of prospective bioactive substituted benzenethiol that have shown significant antimicrobial activity1-2 against some selected strains of fungi, bacteria and lead us to develop a possibly potent class of biologically active agents. Heterocyclic compounds such as 10H-Phenothiazines, 4H,1-4 Benzothiazines and their derivatives sulfones, ribofuranosides etc. used as tranquilizers, antihistamines, diuretics, analgesics, neurolepitcs, sedatives, antipsychotics, CNS depressants, anticancer, antidepressants, antipyretics, antiparkinson drugs3-7 etc. Substituted benzenethiol were prepared from substituted aryl amines. | |||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Keywords | Thiol, Phenylthioureas, Thiazoles, Bilogical Activity. | |||||||||||||||
| Introduction |
In all kinds of organic compounds the presence of heterocycles is very well known i.e. electronics, biology, optics, pharmacology, material sciences etc. Heterocyclic compounds having sulfur and nitrogen atoms are important template for organic synthesis.
Substituted benzenethiols and their derivatives may increase the permeability of the cell wall envelope and bind tightly to eukaryotic and microbial DNA thus presumably inhibiting their replication. The derivatives of substituted benzenethiols8-11 are also used for their cancer chemo preventive effect, neuroleptic action connected with the dopaminergic receptors blockade and protein kinase C inhibitory actions, inhibition of P-glycoprotein transport function and reversion of multidrug resistance12.
Various methods are studied in literature for the synthesis of 2-aminobenzenethiols such as Herz method, Reduction of bis(o-nitrophenyl) disulfides, Thiocyanogenation etc. Some drawbacks have also been detected in these methods. Therefore, only those 2-aminobenzothiazoles which have a substitute at para position undergoes hydrolytic cleavage to synthesize 2-aminobenzenethiols.
|
|||||||||||||||
| Aim of study | In last few decades a considerable amount of attention has been focused on synthesis of nitrogen and sulfur containing heterocycles The investigation of substituted substituted aminobenzenethiols has steadily flourished because they exhibit a large scope of applications. Due to the pharmaceutical properties, substituted aminobenzenethiols are used for clinical purposes, like sedative, antihelmintics, antiinflammatory, antimalarials, antibacterial, anticonvulsants, pesticides etc. Slight change in substitution pattern in substituted aminobenzenethiols nucleus causes distinguishable difference in their biological activities. | |||||||||||||||
| Review of Literature | Arun Goyal, Shikha Agarwal and D.C.Gautam, Indian Journal of
Chemistry, 2022 in the article " different novel 10H-phenothiazines,
their sulfones and ribofuranosides were synthesized using commercially available starting materials
and identified by spectral analysis and have shown moderate to significant
antimicrobial properties. The different bacterial and fungal strains showed
different susceptibility towards the tested compounds, which may be possibly
explained by different resistance mechanism exhibited by each strain. The MIC values of antibacterial and antifungal screening
revealed that the excellent antibacterial and antifungal activities against all
the three selected strains of bacteria and fungi respectively". Nishidha Khandelwal, Abhilasha Yadav et al., Nucleosides Nucleotides Nucleic Acids, 2012 in the article "Synthesized phenothiazines on oxidation with 30% hydrogen peroxide in glacial acetic acid yield sulfones, and when treated with sugar give ribofuranosides. These compounds are evaluated for their anthelmintic and antimicrobial activities. |
|||||||||||||||
| Methodology | A mixture of concentrated hydrochloric acid (9 ml) and water (25 ml) with substituted aniline (I) (0.1 mole), were taken in a 250 ml R.B. flask, and heated for half an hour, and then 0.1 mole ammonium thiocyanate was added and refluxed. Solid phenyl thiourea (II) separated out was filtered. washed with water, dried and crystallized from ethanol.
0.1 Mole synthesized substituted phenylthiourea (II) and Bromine (0.1 mole) in chloroform (100 ml) were taken in a two necked R.B. flask (500 ml) well equipped with a mechanical stirred and the temperature was maintained below 5°C. The reaction mixture was refluxed until the evolution of hydrogen bromide vapors ceased (about 4 hrs). Solid substituted 2-aminobenzothiaozole ( 2-Amino-3,5-dichloro-6-fluoro-benzenethiol) was treated with sulfur dioxide water and filtered.
|
|||||||||||||||
| Analysis |
Table- Biological Activity of Substituted 2-aminobenzenethiol:
|
|||||||||||||||
| Result and Discussion | Spectral assessment
and physical data of the synthesized substituted 2-aminobenzothiaozole
given below. 2-Amino-3,5-dichloro-6-fluoro-benzenethiol Yield 68%, m.p. 92°C,
color: brown; IR (KBr, v): 3450, 3290, 2590, 780 cm–1. 1H NMR (300.40 MHz, DMSO-d6): d 7.79 (s, 1H, Ar-H), d 4.35 (s, 2H, -NH2) d 1.76 (s, 1H, -SH). 13C NMR (75.45 MHz, CDCl3,): d 120.7 (C-1),
129.5 (C-2), 128.4 (C-3), 144.2 (C-4), 128.3
(C-5), 124.8(C-6). "Anal. Calcd for C6H4Cl2FNS: C, 33.96; H,
1.88; N, 6.60; Found : C, 33.45; H, 6.25; N, 6.84". Biological Activity
The synthesized
substituted 2-aminobenzenethiol found active in primary screening were further
tested in a second set of dilution against microorganisms. This substituted
2-aminobenzenethiol were diluted. The highest dilution showing at least 99%
inhibition was taken as MIC. Antibacterial activities11 of the bacterial strains were carried out in Luria broth
(Himedia) medium and all fungi were cultivated in Sabouraud Dextrose Agar
(Himedia) at pH 6.9 by the spectrophotometric method and serial dilution
followed by incubated on a rotary shaker at 37°C. At the end of incubation
period, MIC values were recorded. |
|||||||||||||||
| Conclusion | In the present study, a novel substituted 2-aminobenzenethiols was synthesized using commercially available starting materials and identified by spectral analysis and have shown moderate to significant biological properties. The different bacterial and fungal strains showed different susceptibility towards the tested compound, which may be possibly explained by different resistance mechanism exhibited by each strain. The MIC values of antibacterial screening (2-Amino-3,5-dichloro-6-fluoro-benzenethiol show 128 mg/ml against Escherichia coli MTCC 2939, 116 mg/ml against Bacillus subtilis MTCC 441 and 118 mg/ml against Streptomyces griseus MTCC 1998) revealed that the moderate antibacterial activities against all the three selected strains of bacteria was exhibited by compound. The motive of our research is to extend the area of research by synthesizing new and better templates of 2-aminobenzenethiols and screening them as potential antibacterial drugs but further biomedical research is required. | |||||||||||||||
| Acknowledgement | The authors are very thankful to the Department of Chemistry, Govt. P.G. College, Rajgarh (Alwar), Department of Chemistry, University of Rajasthan, Jaipur as well as Institute of Seminal Applied Sciences, Jaipur for providing necessary facilities and assistance. | |||||||||||||||
| References | 1. J.N. Dominguez , S. Lopez, J. Charris, L. Iarruso, G. Lobo, A. Semenow, J.E. Olson, P.J. Rosenthal, J. Med. Chem. 2726 (40) 1997.
2. G. Lin, K.K. Midha, E.M. Hawes, J. Heterocycl. Chem., 215 (28), 1991.
3. H.N. Dogan, A. Duran, S. Rollas, G. Sener, M.K. Uysal, D. Gulen, Bioorg. Med. Chem. 2893(10), 2002.
4. K. Zamani, K. Faghihi, T. Tofighi, M.R. Shariatzadeh, Turk. J. Chem. 95 (28), 2004.
5. Y. Dixit, R. Dixit, N. Gautam, D.C. Gautam, Nucleos. Nucleot. Nucl. 998(28), 2009.
6. N. Gautam, N. Ajmera, S. Gupta, P. Meena, A. Kumar, D.C. Gautam, Phosphorus, Sulfur Silicon Relat. Elem. 2409 (185), 2010.
7. P. Sarmiento Gabriela, G. Vitale Roxana, Afeltra Avier, Y. Moltrasio Graciela, G. Moglioni Albertina, Eur. J. Med. Chem.101 (46), 2019.
8. B.S. Rathore, M. Kumar, R.R. Gupta, Bioorg. Med. Chem. 5678 (14), 2006.
9. N. Khandelwal, Abhilasha, N. Gautam, D.C. Gautam, J. Chem. Sci. 85 (125) 2013.
10. N. M. Bayoumy, A. Fekri, E. H. Tawfik, A. A. Fadda, Polycycl Aromat Compd. 2019.
11. H. Kawamura, M. Arai, A. Togari, J Pharmacol Sci. 117(54) 2011.
12. A. Jaszczyszyn, K. Gąsiorowski, P. Świątek, W. Malinka, K. Cieślik-Boczula, J. Petrus, B. Czarnik-Matusewicz, Pharmacol Rep. 16 (64), 2012.
13. Arun Goyal, Shikha Agarwal, D.C. Gauttam, Indian J. Chem. 61 (842-848) 2022 |
|||||||||||||||
