A REVIEW ON PYRAZOLINE DERIVATIVES AS ANTIMICROBIAL AGENT

At present, there is a lot of research about the pyrazoline heterocyclic compound, its ring structure is being changed and new derivatives are being made, many of which have antimicrobial activity over the derivatives. Pyrazoline is the five-member heterocyclic ring which have two N atoms in nearby position and contains two endocyclic double bonds. Noteworthy consideration has been concentrated on pyrazolines and pyrazoline derivative due to their important pharmacological action. Some replaced pyrazolines have been stated near retain particular important pharmacological actions as antimicrobial, antifungal, antineoplastic, antidepressant, insecticidal, anticonvulsant, anti-inflammatory, antibacterial and antitumor properties.


INTRODUCTION
Microbial Infections (fungal and bacterial) have been informed to rise affected globally in present days and main causes are toward the block resistance. Both hospitalized and ambulatory patients are very needful of antimicrobials widespread. It is described that 24% to 40.8% of hospitalized persons accept them [1]. Destruction of resistance owing to several causes such as distortion, operations, immunosuppressive treatments, old age, HIV infection, is a reasonable sources that seats patients at great risk for transmittable contagious contaminations. This condition is exacerbated through growing rate of microbial conflict to the general antibiotics existing nowadays [2]. Antimicrobial altercation is a main anxiety, the threat to the community health in addition permits improvement and development of new and active antibiotics to challenge drug quarrel. To reveal these matters, there is a essential to develop new insignificant, harmless and effective drugs with a wide range of antimicrobial action [3]. There are several heterocyclic ring compounds having nitrogen atom such as pyrazole, pyrrolones, pyridazinones, pyrazolines have been considered generally used for the improvement of essential antimicrobial action. The powerful new drugs must been displayed to save lives when used to give some severe infections and to reduce the trouble of illness when used prophylactically in certain clinical situation. For the synthesis of new antibiotics, researcher effort lots on chemical compounds and pyrazoline derivatives are valuable as antimicrobial agents. Pyrazolines are enormously valuable nitrogen-containing heterocyclic compounds that occur in a diversity of chemical and biological agents and improve their activities. N-N bond of the pyrazoline ring is restrained to be the important cause in their biological activities [4]. Pyrazoline can be defined as dihydro pyrazole having only one endocyclic double bond. On the basis of the position of the double bond three types of pyrazoline are possible: (i) 1-pyrazoline (ii) 2-pyrazoline and (iii) 1, 3-pyrazoline, 2pyrazoline is most attractive and important among all type of pyrazolines for frequent studies.

Fig. 1: Types of pyrazoline
Actually, pyrazolines are the reduced forms of pyrazoles, while pyrazolidine is a completely reduced form of pyrazole.

Fig. 2: Hydrogenation of pyrazole to pyrazoline then pyrazolidine
Pyrazoline derivatives have been found in natural products in the form of vitamins, alkaloids, and pigments.
Pyrazoline end products were stated to retain a number of evident pharmacological activities, antimoebic, antimicrobial, antibacterial, antidepressant, antitubercular, antifungal, antiviral, anticancer, anticonvulsant. Some of the modern drugs of the pyrazoline nucleus include Phenazone, Metamizole, Aminopyrine, Phenylbutazone, Sulfinpyrazone, Oxyphenbutazone and Celecoxib. The literature search was steered using accessible databases, including ScienceDirect, PubMed, Scopus and Google Scholar. The dissertations, thesis, books and technical reports were also combed. The objective of this review is to provide all the literature of approximately fifteen years.

Fig. 12: Novel 1, 3, 5-triphenyl-2-pyrazoline derivatives
Venkataraman et al. (2010) synthesized some new pyrazoline derivatives from Chalcones. Which may be synthesized by different acetophenones react with different benzaldehydes to give chalcone, which on condensed with hydrazine hydrate in ethanol to acquire pyrazoline derivatives. All derivatives were tested for in vitro antibacterial and anti-inflammatory activities. All synthesized derivatives were confirmed activity against S. aureus, B. subtilis, E. coli, P. aureginosa. Some of the new derivatives exhibited promising anti-inflammatory activities [18].

Fig. 21: Quinazolinyl 2-pyrazolines
Ishwar Bhat et al. (2014) were reported that the reactions of chalcones with aryloxy acetyl hydrazines yield (70-80%) 1, 3, 5 substituted pyrazoline derivatives in the presence of glacial acetic acid. Synthesized compounds were screened for antibacterial, antifungal and antitubercular activity studies. Synthesized compounds showed significant activity against ampicillin and moderate to significant antifungal activity against griseofulvin. Antibacterial activity studies revels that good antitubercular activities against isoniazid as a standard drug [28].  Fumigatus, A. versicola) at the conc. of 12.5µg/ml compared with standard drug fluconazole. All compounds display moderate to potent antifungal activity [30].

Fig. 24: Disubstituted pyrazoline derivatives
Parajuli et al. (2015) reported that the reaction of chalcones with phenylhydrazine results a novel 3-phenyl-5-(4-dimethylaminophenyl)-1-phenyl-pyrazolone. The synthesized compounds were tested against S. faecalis, S. aureus and E. coli for their antibacterial activity by disc diffusion method. The researcher concluded on the basis of antibacterial evaluation data that the synthesized new compounds showed sufficient antibacterial activity towards S. aureus [31].

Fig. 25: Novel 3-phenyl-5-(4-dimethylaminophenyl)-1-phenylpyrazoline
Sulthana et al. (2015) reported a research paper on design and synthesis a new series of thiophene and benzodioxole appended thiazolyl-pyrazoline derivatives by the microwave-assisted method and screened for antimicrobial potency against different bacteria and fungi. Few compounds show good antimicrobial potency [32].   The synthesized compounds were subjected for antimicrobial activity [35].

Fig. 29: 3-(Aryl)-5-[4-(2,4-Dichlorophenylmethoxy)-3methoxyphenyl]-4,5-dihydro pyrazoline
Ahmed et al. (2016) reported the synthesis of two series of pyrazoline derivatives beginning from p-acetamidophenol (paracetamol) and screened for antimicrobial activity. Chalcones were prepared by reacting 3-acetyl-4-hydroxyphenyl acetamide with different aromatic aldehydes. These chalcones were further reacted with phenylhydrazine and isoniazid to get phenylpyrazolines and isoniazid-pyrazolines. New pyrazoline derivatives displayed important antibacterial potency against E. coli, S. aureus, and P. aeruginosaas compared using the standard antibiotic ciprofloxacin. In the conclusion found that some derivatives possesses powerful antibacterial activity against S. aureus, P. aeruginosa and at the conc. of 3.12 mg/ml [36]. All metal complexes structures were analytically confirmed by IR, NMR, Mass, ESR spectroscopy and elemental analysis. All synthesized derivatives were screened against bacterial strains E. coli, S. aureus, K. pneumoniae, Proteus mirabilis and S. typhii as compared to the standard drug streptomycin. All compounds also were estimated for in vitro antimycobacterial activity against Mycobacterium tuberculosis [37].    Desai et al. (2017) synthesized few novel derivatives of (5-(2chloroquine in-3-yl)-3-(aryl)-4, 5-dihydro-1H-pyrazol-1-yl)(pyridin-4-yl) methanones moieties embedded in different biologically active heterocyclic compounds e. g. pyrazoline quinoline and pyridine derivatives. Reported compounds were analytically determined by spectrometric methods like IR, 1 H NMR, [13]C NMR, Mass spectra. These compounds were screened for antimicrobial activity on four strains of bacteria (S. aureus, S. pyogenes, E. coli, P. aeruginosa) and three strains of fungi (C. albicans, A. niger, A. clavatus) using griseofulvin and ampicillin as the standard drugs [43].  The new compounds were screened for in vitro, antimicrobial activity against some pathogenic microbial strains [46]. The synthesized compounds have been identified by their melting point, TLC, IR and NMR spectral data. All the synthesized compounds have been evaluated for antibacterial potential against gram-positive bacterial strains, B. subtillis and B. pumilus and gram-negative bacterial strains E. coli and P. vulgaris and antifungal activity against fungal strains, A. niger and p. crysogenium [47]. All the compounds were evaluated for antibacterial activity against gram-positive strains (S. Aureus, B. Subtilis) and gram negative strains (E. coli, K. Pneuminoae) at suitable conc. as compared to standard drug ciprofloxacin. All the compounds showed moderate to potent antibacterial activity [48].  (bacteria and fungi) were taken for antimicrobial activities of synthesized compounds as compared to standard drugs streptomycin and ketoconazole at the MIC conc. from 0.039-0.312 mg/ml [50].
Asad et al. (2020) synthesized a series of N-propionyl 2-pyrazolines from the chalcones by reacting propionic acid with hydrazine hydrate. The atomic structure of new pyrazoline derivatives were confirmed by FT-IR, NMR spectroscopy, crystal structure, X-ray diffraction techniques. All new compounds were evaluated for antibacterial activity against gram-positive bacterial strain (B. Subtilis, S. Aureus) and gram-negative bacterial strain (E. Coli, P. Peli).
All new compounds display significant activity against bacteria [52]. The objective of this review is to provide a platform for researcher, academician, chemist and industrialists to have all the information regarding the antimicrobial activity of pyrazoline. Various synthetic routes were discussed with its chemistry. The literature eliciting the antimicrobial activity were discussed. As the literature shows that there is always demand of novel antimicrobial agents due to the pathogen resistance. So, this literature would be fruitful to the society as well. This would provide the researcher a lead that they may come with a new and potent pyrazoline bearing derivative.