Development of 5-(Aryl)-3-phenyl-1H-pyrazole Derivatives as Potent Antimicrobial Compounds

Abstract

INTRODUCTIONChalcones (1) and pyrazoles (2) are the most important classes of flavonoids and alkaloids respectively present across the whole plant kingdom [1,2]. Both have interesting bioactive features associated with several biological activities. Chalcones and their derivatives demonstrate wide range of biological activities such as antidiabetic, antineoplastic, antihypertensive, antiretroviral, anti-inflammatory [3], antiparasitic [4], antihistaminic [5], antimalarial [6], antioxidant [7], antifungal [8], antiobesity [9], antiplatelet [10], antitubercular [11], immunosuppressant [12] etc. Also, pyrazole nucleus has found considerable attention due to its potent medicinal scaffolds and exhibits full spectrum of biological activities. Many pyrazole derivatives have already found their application as antimicrobial [13-16], antifungal [17], anticancer [18-20], anti-inflammatory [13,21-26], antiviral [14], antioxidant [27], etc.Chalcone is an acyclic compound with substituted aromatic ring at both side of the double bond which allows the molecule to adopt many conformations due to weak π-π interactions A series of 16 chalcone compounds were synthesized by Claisen-Schmidt condensation of various aldehydes with acetophenone using KOH as a base in ethanol. The reaction affords the desired products in good yields. Then all the 16 compounds were converted into pyrazoles by treating with hydrazine hydrate in ethanol under reflux condition. Both chalcones and pyrazoles were screened for their in vitro antibacterial (Escherichia coli, Staphylococcus aureus and Pseudomonas aeruginosa) and antifungal (Aspergillus flavus, Chrysosporium keratinophilum and Candida albicans) activity. Biological activities of these compounds were compared with those of commercially available antibiotic ampicillin and antifungal agent miconazole. Pyrazoles were found to be most active and effective than corresponding chalcones for antimicrobial activity. Out of the 7 pyrazole compounds tested for antibacterial and antifungal activity, 5 compounds, 4h, 4j, 4l, 4m and 4n are turned out to be potent antimicrobial agents. Therefore these derivatives could serve as a highly promising molecules for further development.

Pyrazoles as Key Scaffolds for the Development of Fluorine-18-Labeled Radiotracers for Positron Emission Tomography (PET)

“…They demonstrated that pyrazole (1,2-diazole) can be used to Pyrazole derivatives act on diverse and relevant biological targets, which make them attractive for the development of PET tracers, and possess a wide range of pharmaceutical activities. Abdel-Maksoud et al have demonstrated antitumoral activity of several compounds with a pyrazole and sulfonamide moieties [19]; antibacterial and antifungal activity of pyrazole was demonstrated by Chowdary et al [20]. Pyrazoles also showed good activity as monoamine oxidase inhibitors, antidepressant and anticonvulsant agents [21], as BRAF inhibitors [22] and DNA gyrase inhibitors [23] and present antileishmanial, anti-inflammatory, analgesic, antidiabetic and cannabinoid activity; cyclin-dependent kinase and tissue-nonspecific alkaline phosphatase inhibitory activity and moderate antihepatotoxic activity, among others [9,11,[24][25][26][27][28][29].…”

Revisiting the Chemistry of Vinylpyrazoles: Properties, Synthesis, and Reactivity

“…Pyrazoles have attracted increased attention in recent years owing to their widespread applications in medicine [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 ], agriculture, [ 16 ] materials science [ 17 , 18 , 19 , 20 ], and catalysis [ 21 , 22 ]. In this review, the chemistry of a particular kind of pyrazoles, the vinylpyrazoles, is revisited.…”

Styrylpyrazoles: Properties, Synthesis and Transformations

“…Three partially reduced forms may also exist: 1-pyrazolines 2, 2-pyrazolines 3 and 3-pyrazolines 4, and a fully reduced form known as pyrazolidine 5 (Figure 1) [1,2]. Pyrazole and its derivatives occupy a prime place in medicinal chemistry because they are present in several drugs with real medicinal applications, such as celecoxib (Celebrex ® ), sildenafil (Viagra ® ), rimonabant, lonazolac, fomepizole, penthiopyrad, doramapimod, sulfaphenazole and in several remarkable compounds with a wide range of pharmacological activities, namely anticancer [3], analgesic, anti-inflammatory and antioxidant [4][5][6][7], antibacterial and antifungal [8,9] antipyretic, antidepressant and anticonvulsant [10,11], antidiabetic [12] and cannabinoid activities [13,14], among Pyrazole and its derivatives occupy a prime place in medicinal chemistry because they are present in several drugs with real medicinal applications, such as celecoxib (Celebrex ® ), sildenafil (Viagra ® ), rimonabant, lonazolac, fomepizole, penthiopyrad, doramapimod, sulfaphenazole and in several remarkable compounds with a wide range of pharmacological activities, namely anticancer [3], analgesic, anti-inflammatory and antioxidant [4][5][6][7], antibacterial and antifungal [8,9] antipyretic, antidepressant and anticonvulsant [10,11], antidiabetic [12] and cannabinoid activities [13,14], among others [15][16][17][18][19][20][21]. Along with the medicinal applications, pyrazoles are also useful as agrochemicals, such as herbicides, others [15]…”

“…Pyrazole and its derivatives occupy a prime place in medicinal chemistry because they are present in several drugs with real medicinal applications, such as celecoxib (Celebrex ® ), sildenafil (Viagra ® ), rimonabant, lonazolac, fomepizole, penthiopyrad, doramapimod, sulfaphenazole and in several remarkable compounds with a wide range of pharmacological activities, namely anticancer [ 3 ], analgesic, anti-inflammatory and antioxidant [ 4 , 5 , 6 , 7 ], antibacterial and antifungal [ 8 , 9 ] antipyretic, antidepressant and anticonvulsant [ 10 , 11 ], antidiabetic [ 12 ] and cannabinoid activities [ 13 , 14 ], among others [ 15 , 16 , 17 , 18 , 19 , 20 , 21 ]. Along with the medicinal applications, pyrazoles are also useful as agrochemicals, such as herbicides, fungicides, and insecticides [ 22 ] and possess other applications, such as dyestuffs, sunscreen materials [ 23 , 24 ], analytical reagents and pluripotent ligands in coordination chemistry [ 25 , 26 ].…”