Research Article | Volume: 9, Issue: 12, December, 2019

Novel 4-hydroxy-N'-[(1E)-substituted-phenylmethylidene] benzohydrazide analogs (hydrazones) as potent antibacterial and anti-oxidant agents

Jasmine Chaudhary Akash Jain Rohini Manuja   

Open Access   

Published:  Dec 03, 2019

DOI: 10.7324/JAPS.2019.91203
Abstract

In the present study, a series of 4-hydroxy-Nʹ-[(1E)-substituted-phenylmethylidene] benzohydrazide analogs was synthesized, characterized, and evaluated for their antibacterial and anti-oxidant activity. All the tested compounds show high antibacterial activity with compound AR7, Nʹ-(3,4,5-trimethoxybenzylidene)-4-hydroxybenzohydrazide as the most active compound, whereas compounds AR10 (hydrogen peroxide scavenging) and AR8 (2,2-diphenyl-1- picrylhydrazyl radical scavenging activity method) were found to possess maximum anti-oxidant activity indicating that different mechanisms are involved in different anti-oxidant determination methods.


Keyword:     Synthesis hydrazones antibacterial antioxidant.


Citation:

Chaudhary J, Jain A, Manuja R. Novel 4-hydroxy-N'-[(1E)- substituted-phenylmethylidene] benzohydrazide analogs (hydrazones) as potent antibacterial and anti-oxidant agents. J Appl Pharm Sci, 2019; 9(12):015–020.

Copyright: © The Author(s). This is an open-access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

HTML Full Text

INTRODUCTION

Multi-drug resistant microbial infection, a major problem in the treatment of infectious disease, is increasing considerably from the last decades (Ahmad et al., 2012; Makki et al., 2015) and to overcome this problem, development of new antimicrobial agents is the need of the hour (Lindahl, 2015; Venkatesh et al., 2016). Hydrazones, belonging to Schiff base family with chemical formula R2C=NNR2, are of incredible interest because of their various biological activities reported in literature, viz., anti-bacterial, anti-fungal, anti-convulsant, anti-inflammatory, anti-cancer, anti-viral, anti-malarial & anti-tuberculosis, anti-oxidant, and antidepressant (Alam et al., 2012; Kumar and Chauhan, 2014; Marwa and Ahmed, 2018; Neda et al., 2018; Nurkenov et al., 2017; Popiolek, 2017; Rayam et al., 2015; Verma et al., 2014). Along with the diverse activities, their ease of synthesis, increased stability, and tendency toward crystallinity make hydrazones a perfect choice to synthesize more effective and novel antimicrobial agents (Bala et al., 2011; 2013; Singh et al., 2016).

The antimicrobial (Chaudhary et al., 2008; Kapoor and Dahiya, 2016; Khatkar et al., 2017) and anti-oxidant (Velika and Kron, 2012; Pontiki and Litina, 2019) perspective of organic acids can be well recognized from the literature. Phenolic compounds (Abouzeed et al., 2018; Benslama et al., 2017; Fu et al., 2016; Sahloul et al., 2014) are also proved as successful antibacterial as well as anti-oxidant activity which might be due to the fact that anti-oxidants act by creating scavenging environment which may inhibit bacterial growth. p-hydroxy benzoic acid, a phenolic derivative, is also found to possess various pharmacological activities, viz., antimicrobial, antialgal, antisickling, antimutagenic, antiviral, anti-inflammatory, anti-oxidant, etc., (Manuja et al., 2013). Antimicrobial potential of p-hydroxy benzoic acid derivatives, viz., Nʹ-(4-methoxybenzylidene)-4-hydroxybenzohydrazide, Nʹ-benzylidene-4-hydroxybenzohydrazide have also been reported (Sapra et al., 2014; Suzana et al., 2017). Therefore, the present study was designed with the aim of synthesizing novel hydrazone derivatives of p-hydroxy benzoic acid for exploring their antimicrobial and anti-oxidant potential.


MATERIALS AND METHODS

Ester of 4-hydroxy benzoic acid was synthesized using Fischer esterification which was further treated with hydrazine hydrate in ethanol to yield corresponding 4-hydroxybenzoic acid hydrazides. The synthesized hydrazides were further reacted with substituted aldehydes (aromatic) in presence of glacial acetic acid (2–3 drops) to yield 4-hydroxy-Nʹ-[(1E)-substituted phenylmethylidene] benzohydrazide (AR1–AR10) (Scheme 1) which were then characterized by spectral and analytical means (Harer et al., 2010; Narang et al., 2012; Rajput and Rajput, 2009).

Evaluation of antibacterial activity

Antibacterial activity of synthesized products was evaluated against Escherichia coli (ATCC 25922), Pseudomonas aeruginosa (ATCC 27853), Staphylococcus aureus (ATCC 25923), and Enterococcus faecalis (ATCC 29212) using Norfloxacin standard as it is the most widely used antibiotic in bacterial infections (Table 2) (Cappucino and Sherman, 1999) by tube dilution method using double strength nutrient broth IP followed by incubation at 37°C ± 1°C.

Antioxidant activity

Hydrogen peroxide radical scavenging (H2O2) assay

Hydrogen peroxide plays an important role as bactericidal agent (Halliwell, 1995) by acting directly or indirectly via its reduction product, OH- (second messenger in synthesis and activation of several inflammatory mediators) (Sprong et al., 1998).

Anti-oxidant activity by the H2O2 method was determined as per the method reported (Ruch et al., 1989). Different dilutions of synthesized (20–60 μg/ml), as well as standard compound (Ascorbic acid) in distilled water, were added to 40 mM H2O2 solution prepared in phosphate buffer and absorbance was measured at 230 nm after 10 minutes against a blank solution.

DPPH radical scavenging activity

DPPH radical scavenging, a standard rapid assay for antioxidant studies (Soares et al., 1977), was done by adding ethanolic DPPH solution (0.1 Mm) to test solutions as well as standard compound to make different dilutions (20–60 μg/ml) and then by measuring their absorbance at 517 nm after 30 minutes. Scavenging activity in both methods was expressed as inhibition percentage and calculated using the following formula:

% inhibition = (AoAt)/ Ao × 100

where Ao is the absorbance control (blank); At is the absorbance of the test (Shukla et al., 2009).

Scheme 1. Synthesis of 4-hydroxy-N'-[(1E)-substituted-phenylmethylidene] benzohydrazide analogs.

[Click here to view]


RESULTS AND DISCUSSION

Melting points of synthesized compounds were determined (Elico melting point apparatus, India) and purity was ascertained using single spot TLC (Table 1). The structures were confirmed by spectral studies (IR spectra on FTIR-Shimadzu spectrometer and 1H NMR spectra on BRUKER AVANCE II 400 NMR spectrometer using DMSO). The data obtained from spectral studies were in agreement with assigned molecular structures.

Analytical data for compound AR1

M.P.(°C): 243–247; Yield: 77.4%; IR (cm−1): 1,738.90 (C=O stretch), 1,627.99 (C=N stretch), 3,731.45 (OH stretch), 1,547.47 (C=C stretch), 3,227.35 (NH stretch), 2,995.45 (C-H stretch) ; 1H NMR: (δ) 9.9 (s, 1H, N=CH), 8.4 (s, 1H, NH-N=), 7.8 (d, 2H, Ar-H), 7.5 (m, 2H, Ar-H), 7.4 (m, 3H, Ar-H), 6.9 (m, 2H, Ar-H), 5.2 (s, 1H, OH).

Analytical data for compound AR2

M.P.(°C): 211–214; Yield: 72%; IR (cm−1): 1,720.13 (C=O stretch), 1,625.98 (C=N stretch), 3,636.48 (OH stretch), 3,279.74 (NH stretch), 3,035.96 (Aromatic CH stretch), 1,521.84 (Aromatic C=C stretch), 671.23 (C-Cl stretch), 2,961.45 (C-H stretch), 630.42 (CH Rocking), 1,148.46 (C-C stretch); 1H NMR: (δ) 9.1 (s, 1H, -NH-N=), 8.1 (s, 1H, -N=CH-), 7.8 (d, 2H, Ar-H), 7.6 (d, 2H, Ar-H), 7.3 (d, 2H, Ar-H), 6.9 (d, 2H, Ar-H), 5.4 (s, 1H, OH).

Analytical data for compound AR3

M.P. (°C): 225–227; Yield: 56.5%; IR (cm−1): 1,706.11 (C=O stretch), 1,665.45 (C=N stretch), 3,715.31 (OH stretch), 3,269.13 (NH stretch), 3,056.34 (Aromatic CH stretch), 1,504.54 (Aromatic C=C stretch), 2,921.32 (C-H stretch), 640.39 (CH Rocking), 1,148.46 (C-C stretch); 1H NMR: (δ) 8.0 (s, 1H, -NH-N=), 8.1 (s, 1H, -N=CH), 7.8 (d, 2H, Ar-H), 7.5 (d, 2H, Ar-H), 7.1 (d, 2H, Ar-H), 6.9 (d, 2H, Ar-H), 5.1 (s, 1H, OH).

Analytical data for compound AR4

M.P. (°C): 170–173; Yield: 55.3%; IR (cm−1): 1,717.68 (C=O stretch), 1,627.99 (C=N stretch), 3,558.27 (OH stretch), 3,237.65 (NH stretch), 1,573.98 (NH band), 3,024.51 (Aromatic CH stretch), 1,544.08 (Aromatic C=C stretch), 1,302.01 (C-O stretch), 3,042.44 (C-H stretch), 659.68 (CH Rocking). 1,023.28 (C-C stretch); 1H NMR: δ 9.2 (s, 1H,-NH-N=), 8.1 (s, 1H,-N=CH-), 7.8 (d, 2H, Ar-H), 7.0 (m, 2H, Ar-H), 6.9 (d, 2H, Ar-H), 6.7 (d, 2H, Ar-H), 5.6 (s, 1H, OH), 3.7 (s, 3H, -OCH3).

Analytical data for compound AR5

M.P. (°C): 247–249; Yield: 67.9%; IR (cm−1): 1,710.70 (C=O stretch), 1,638.00 (C=N stretch), 3,562.60 (OH stretch), 1,560.92 (NH band), 3,081.60 (Aromatic CH-stretch), 1,590.92 (NH band), 1,545.65 (C=C stretch), 636.51 (CH rocking); 1H NMR: δ 9.8 (s,1H,NH), 8.4 (s,1H,OH), 7.8 (d, 2H, Ar-H), 7.7 (d, 2H, Ar-H), 7.6 (d, 2H, Ar-H), 7.3 (d, 2H, Ar-H), 7.1 (d, 2H, Ar-H), 7.0 (s, 1H, OCH3), 6.8 (d, 2H, Ar-H).

Analytical data for compound AR6

M.P. (°C): 177–177; Yield: 87.8%; IR (cm−1): 1,690.68 (C=O stretch), 1,636.67 (C=N stretch), 3,554.41 (OH stretch), 3,277.20 (NH stretch), 3,037.05 (Aromatic CH stretch), 1,540.23 (Aromatic C=C stretch), 1,092.72 (C-O stretch), 2,772.79 (C-H stretch), 659.68 (CH Rocking), 1,033.89 (C-C stretch); 1H NMR: δ 8.0 (s, 1H, -NH-N=), 8.1 (s, 1H, -N=CH-), 7.7 (d, 2H, Ar-H), 7.1 (m, 2H, Ar-H), 7.2 (m, 2H, Ar-H), 6.9 (d, 2H, Ar-H), 5.4 (s, 1H, OH), 3.7 (s, 3H, -OCH3).

Table 1. Physical data of synthesized derivatives.



[Click here to view]

Table 2. Antibacterial activity of synthesized compounds.



[Click here to view]

Analytical data for compound AR7

M.P. (°C): 164–168 (°C); Yield: 74.9%; IR (cm−1): 1,730.11(C=O stretch), 1,690.25(C=N stretch), 3,675.15(OH stretch), 3,234.45 (NH stretch), 3,024.11 (Aromatic CH stretch), 1,560.45(Aromatic C=C stretch), 1,290.25 (C-O stretch), 2,755.31(C-H stretch); 1H NMR: δ 10.5 (s, 1H, CH), 9.9 (s, 1H, NH), 7.9 (s, 1H, OH), 6.8 (d, 2H, Ar-H), 3.1 (s, 6H, 2OCH3), 2.4 (d, 2H, Ar-H), 2.2 (s, 3H, CH3).

Analytical data for compound AR8

M.P. (°C): 212–215; Yield: 59.8%; IR (cm−1): 1,690.68 (C=O stretch), 1,691.64 (C=N stretch), 3,758.27 (OH stretch), 3,282.99 (NH stretch), 1,576.87 (NH band), 3,026.44 (Aromatic CH stretch), 1,544.68 (Aromatic C=C stretch), 1,105.26 (C-O stretch), 2,779.54 (C-H stretch), 660.65 (CH Rocking), 1,026.17 (C-C stretch); 1H NMR: δ 9.6(s, 1H, NH), 8.4(s, 1H, OH), 7.8(d, 2H, Ar-H), 7.7(d, 3H, Ar-H), 7.6(d, 2H, Ar-H), 7.5 (d, 2H, Ar-H), 3.2(s, 3H, CH3).

Analytical data for compound AR9

M.P. (°C): 125–128; Yield: 48.1%; IR (cm−1): 1,705.10 (C=O stretch), 1,645.74 (C=N stretch), 3,575.45 (OH stretch), 3,258.90 (NH stretch), 3,021.45 (Aromatic CH stretch), 2,650.45 (C-H stretch), 1,510.64 (Aromatic C=C stretch), 675.71 (CH Rocking). 1,019.21 (C-C stretch); 1H NMR: δ 7.8 (d, 2H, Ar-H), 7.7 (d, 2H, Ar-H), 7.4 (m, 2H, Ar-H), 6.9 (d, 2H, Ar-H), 7.0 (s, 1H, -NH-N=), 5.1 (s, 1H, OH).

Analytical data for compound AR10

M.P. (°C): 112–115; Yield: 97.7%; IR (cm−1): 1,720.18 (C=O stretch), 1,685.71 (C=N stretch), 3,658.27 (OH stretch), 3,368.85 (NH stretch), 3,156.44 (Aromatic CH stretch), 1,642.55 (Aromatic C=C stretch), 1,576.87 (NH band), 3,079.54 (C-H stretch), 742.32 (C-Cl stretch), 670.55 (CH Rocking). 1,026.17 (C-C stretch); 1H NMR: δ 7.8 (d, 2H, Ar-H), 7.3 (m, 2H, Ar-H), 7.2 (m, 2H, Ar-H), 6.9 (d, 2H, Ar-H), 7.0 (s, 1H, -NH-N=), 5.1 (s, H, OH), 1.3 (s, 3H, -CH3)

Antibacterial evaluation

In E. coli, compounds AR7 (pMIC = 1.420) and AR10 (pMIC = 1.412); in P. aeruginosa, compounds AR1 (pMIC = 1.62) and AR6 (pMIC = 1.284); in S. aureus, compounds AR7 and AR8 and in E. faecilis, compounds AR4, AR7, and AR8 were emerged as the most active one.

From antibacterial studies, compound AR7, Nʹ-(3,4,5-trimethoxybenzylidene)-4-hydroxybenzohydrazide in case of E. coli, S. aureus, and E. faecilis and compound AR6, Nʹ-(3-methoxybenzylidene)-4-hydroxybenzohydrazide in case of P. aeruginosa were emerged as the most active compound indicating that methoxy group (e-donating group) on benzene ring is essential for antibacterial activity (Emami et al., 2008). All compounds show good antibacterial property which may be due to the presence of benzylidene/1-phenyl-ethylidene which imparts lipophillicity, a parameter responsible for penetration of molecules across the microbial membrane. In case of E. coli, the compound AR10 containing electron withdrawing chlorine group was also found effective which confirmed the fact that different structural requirements are requisite for activity against different microorganisms (Sortino et al., 2011). The above facts are summarized in Figure 1.

Antioxidant evaluation

To verify the fact that antibacterial compounds also possess anti-oxidant activity, the synthesized compounds were evaluated and it was observed that compound AR10 possesses maximum anti-oxidant activity followed by compounds AR3 and AR7 as governed by hydrogen peroxide scavenging activity method, whereas in DPPH scavenging activity, compound AR8 possesses maximum antioxidant activity followed by compound AR9 > AR10. All these compounds show even better antioxidant activity than reference compound Ascorbic acid as depicted by their IC50 (Table 3; Fig. 2a and b)

The high activity of compounds AR2 and AR10 can be explained by the fact that halogens like chloro enhance antioxidant activity due to its redox activity through one electron transfer mechanism (Bala et al., 2012; Dudhe et al., 2013; Hossain et al., 2009). The high activity of compounds AR3, AR7, AR6, AR8, and AR9 can be explained by the fact that methoxy and alkyl/aryl enhanced the stabilization of the generated radical during oxidation (Hadi et al., 2013). There is no correlation between results obtained by both methods, which governs that completely different mechanisms are involved in these two anti-oxidant determination methods.

Figure 1. SAR studies.

[Click here to view]

Table 3. IC50 of synthesized derivatives.



[Click here to view]

Figure 2. (a and b) IC50 of synthesized compounds (H2O2 and DPPH method).

[Click here to view]


CONCLUSION

A series of 4-hydroxy-Nʹ-[(1E)-substituted-phenylmethylidene] benzohydrazide derivatives were synthesized and evaluated for its antibacterial and anti-oxidant activity. Compound AR7 was found most potent antimicrobial against E. coli, S. aureus, E. faecilis, and and compound AR6 against P. aeruginosa which might be due to the presence of methoxy group (electron donating group) on benzene ring indicating the importance of electronic parameters in governing potency. Compounds AR10 and AR8 show maximum anti-oxidant activity when governed by hydrogen peroxide and DPPH scavenging activity, respectively, signifying different mechanisms are involved in antioxidant determination.


ACKNOWLEDGMENT

The authors would like to thank the M. M. College of Pharmacy, M. M. (Deemed to be University), Mullana, Ambala for providing support and facility to carry out research.


CONFLICT OF INTEREST

The authors declared no conflict of interest.


FUNDING

None.


REFERENCES

Abouzeed YM, Zgheel F, Elfahem AA, Almagarhe MS, Dhawi A, Elbaz A, Hiblu MA, Kammon A, Ahmed MO. Identification of phenolic compounds, antibacterial and antioxidant activities of raisin extracts. Open Vet J, 2018; 8(4):479–84. CrossRef

Ahmad Al, Ahmad E, Rabbani G, Haque S, Arshad M, Khan RH. Identification and design of antimicrobial peptides for therapeutic applications. Curr Protein Pept Sci, 2012; 13(3):211–23. CrossRef

Alam M, Ali R, Marella A, Alam T, Naz R, Akhter M, Shaquiquzzaman M, Saha R, Tanwar O, Hooda J. Review of biological activities of hydrazones. Indonesian J Pharm, 2012; 23(4):193–202.

Bala S, Uppal G, Kajal A, Kamboj S, Sharma V. Hydrazones as promising lead with diversity in bioactivity-therapeutic potential in present scenario. Int J Pharm Sci Rev Res, 2013; 18(1):65–74.

Bala S, Uppal G, Kamboj S, Saini M. Therapeutic review exploring antimicrobial potential of hydrazones as promising lead. Der Pharma Chemica, 2011; 3(1):250–68.

Bala S, Uppal G, Kamboj S, Saini V, Prasad DN. Design, characterization, computational studies and pharmacological evaluation of substituted-N′-[(1E) substituted phenylmethylidene] benzohydrazide analogs. Med Chem Res, 2012; 21(11):1–13. CrossRef

Benslama A, Harrar A, Gul F, Demirtas I. Phenolic compounds, antioxidant and antibacterial activities of Zizyphus lotus L. leaves extracts. Nat Prod J, 2017; 7(4): 316–22. CrossRef

Cappucino JG, Sherman N. Microbiology—a laboratory manual. Addison Wesley, Redwood City, CA, 1999.

Chaudhary J, Rajpal AK, Judge V, Narang R, Narasimhan B. Preservative evaluation of caprylic acid derivatives in aluminium hydroxide gel–USP. Sci Pharm, 2008;76(3):533–40. CrossRef

Dudhe R, Sharma PK, Dudhe AC, Verma PK. Synthesis and antioxidant activities of 6- Aryl-3,4-dihydro-1-(tetrahydro-3,4-Dihydroxy-5-(hydroxymethyl)-furan-2-yl)-4-phenyl-pyrimidine- 2(1H)-thione derivatives. Eur Chem Bull, 2013; 2(6):341-47.

Emami S, Foroumadi A, Falahati M, Lotfali E, Rajabalian S, Ebrahimi A, Farahyar S, Shafiee A. 2-Hydroxyphenacyl azoles and related azolium derivatives as antifungal agents. Bioorg Med Chem, 2008; 18:141–6. CrossRef

Fu L, Lu WQ, Zhou XM. Phenolic compounds and in-vitro antibacterial and antioxidant activities of three tropic fruits: persimmon, guava and sweetsop. Biomed Res Int, 2016; 2016:9. CrossRef

Hadi A, Alireza F, Reza K, Karim N, Mostafa RT. Synthesis and investigation of antioxidant activities of 2-benzylidene-3-coumaranones. J Paramed Sci, 2013; 4(2):76–81.

Halliwell B, Aerchabach R, Lologer J, Aruoma OI. The characterization of antioxidants. Food Chem Toxicol, 1995; 33(7):601–17. CrossRef

Harer SL, Rajurkar VG, Patil P, Harer PS, Navale SD, Awuti ST, Sonawane AA. Synthesis, characterization and anti-microbial evaluation of some 2- iodo-N'-[(1E)-substituted phenylmethylidene] benzohydrazide analogues. IJPSDR, 2010; 2(2):134–6.

Hossain MM, Shaha SK, Aziz F. Antioxidant potential study of some synthesized N-heterocycles. Bangladesh Med Res Counc Bull, 2009; 35:49–52. CrossRef

Kapoor A, Dahiya SK. Synthesis and evaluation of 2-aryl substituted benzimidazole derivatives bearing 1,3,4-oxadiazole nucleus for antimicrobial activity. Der Pharmacia Lettre, 2016; 8(12):57–67.

Khatkar A, Nanda A, Kumar P, Narasimhan B. Synthesis, antimicrobial evaluation and QSAR studies of p-coumaric acid derivatives. Arab J Chem, 2017; 10(2):S3804–15. CrossRef

Kumar NA, Chauhan LS. Analgesic and anti-inflammatory potential of hydrazones. J Chem Pharm Res, 2014;6(12):916–34.

Lindahl JF, Grace D. The consequences of human actions on risks for infectious diseases: a review. Infect Ecol Epidemiol, 2015; 5(10):3402. CrossRef

Makki MST, Rahman RMA, Ali OAA. Synthesis of new fluorinated 1,2,4-triazino [3,4-b][1,3,4]thiadiazolones as antiviral probes-part II- reactivities of fluorinated 3-aminophenyl-1,2,4-triazinothiadiazolone. Int J Org Chem, 2015; 5(3):1–12. CrossRef

Manuja R, Sachdeva S, Jain A, Chaudhary J. A comprehensive review on biological activities of p-hydroxy benzoic acid and its derivatives. Int J Pharm Sci Rev Res, 2013; 22(2):109–115.

Marwa AM, Ahmed N. Biological activity of some newly synthesized hydrazone derivatives derived from (dicyclopropylmethylene) hydrazone. Eur Chem Bull, 2018; 7(10):280–7. CrossRef

Narang R, Narasimhan B, Sharma S. Synthesis, antimycobacterial, antiviral, antimicrobial activities, and QSAR studies of nicotinic acid benzylidene hydrazide derivatives. Med Chem Res, 2012; 21(9):2526–47. CrossRef

Neda OA, Denista YY, Anelia TM, Magdalena SKB, Virginia IT, Nadya GHA,Vera AH. Design, synthesis, antioxidant properties and mechanism of action of new N,N′-disubstituted benzimidazole-2-thione hydrazone derivatives. J Mol Struct, 2018; 1165:162–76. CrossRef

Nurkenov OA, Satpaeva B, Schepetkin IA, Khlebnikov AI, Turdybekov KM, Seilkhanov TM, Fazylov SD. Synthesis and biological activity of hydrazones of o- and p-hydroxybenzoic acids. Spatial structure of 5-Bromo-2-hydroxybenzylidene-4-hydroxybenzohydrazide. Russ J Gen Chem, 2017; 87(10):2299–306. CrossRef

Pontiki E, Litina DH. Multi-target cinnamic acids for oxidative stress and inflammation: design, synthesis, biological evaluation and modeling studies. Molecules, 2019; 24(1):12. CrossRef

Popiolek L. Hydrazide–hydrazones as potential antimicrobial agents: overview of the literature since 2010. Med Chem Res, 2017; 26(2):287–301. CrossRef

Rajput AP, Rajput SS. Synthesis of benzaldehyde substituted phenyl carbonyl hydrazones and their formylation using Vilsmeier-Haack reaction. Int J PharmTech Res, 2009; 1(4):1605–11.

Rayam P, Anireddy JS, Polkama N, Allakaa TR, Chepurib K, Mukharjee N. Synthesis and biological activity of novel acyl hydrazone derivatives of 3-(4,5-diphenyl1,3-oxazol-2-yl) propanoic acid as anticancer, analgesic and anti-inflammatory agents. J Paramed Sci, 2015; 9(2):157–64.

Ruch RJ, Cheng SJ, Klannig JE. Prevention of cytotoxicity and inhibition of intercellular communication by antioxidant catechins isolated from Chinese green tea. Carcinogensis, 1989; 10:1003–8. CrossRef

Sapra A, Kumar P, Kakkar S, Narasimhan B. Synthesis, antimicrobial evaluation and QSAR studies of p -hydroxy benzoic acid derivatives. Drug Res, 2014; 64:17–22. CrossRef

Shukla S, Mehta A, John J, Singh S, Mehta P, Vyas SP. Antioxidant activity and total phenolic content of ethanolic extract of Caesalpinia bonducella seeds. Food Chem Toxicol, 2009; 47:1848–51. CrossRef

Singh N, Ranjana R, Kumari M, Kumar M. A review on biological activities of hydrazone derivatives. Int J Pharm Clin Res, 2016; 8(3):162–6.

Soares JR, Dinis TCP, Cunha AP, Almeida LM. Antioxidant activities of some extracts of Thymus zygis. Free Radic Res, 1977; 26:469–78. CrossRef

Sortino M, Garibotto F, Cechinel FV, Gupta M, Enriz R, Zacchino S. Antifungal, cytotoxic and SAR studies of a series of N-alkyl, N-aryl and N-alkylphenyl-1,4-pyrrolediones and related compounds. Bioorg Med Chem, 2011; 19(9):2823–34. CrossRef

Sprong RCA, Winkelhuyzen JC, Aarsman J, van Oirschot T, Vandeer B, VanAsbeck B. Low dose N-acetylcysteine protects rats against endotoxin mediated oxidative stress, but high dose increases mortality. Am J Respir Crit Care Med, 1998; 157: 1283–93. CrossRef

Suzana I, Tutuk B. Synthesis, molecular docking and antimicrobial of N’-benzylidene-4-hydroxybenzohydrazide and N’-(4-methoxybenzylidene)-4-hydroxybenzohydrazide. RJPBS, 2017; 8(2):1354–61.

Velika B, Kron I. Antioxidant properties of benzoic acid derivatives against superoxide radical. Free Radical and Antioxidants. 2012; 2(4):62–7. CrossRef

Venkatesh T, Bodke YD, Kenchappa R, Telkar S. Synthesis, antimicrobial and antioxidant activity of chalcone derivatives containing thiobarbitone nucleus. Med Chem, 2016; 6: 440–8. CrossRef

Verma G, Marella A, Shaquiquzzaman M, Akhtar M, Ali MR, Alam MM. A review exploring biological activities of hydrazones. J Pharm Bioallied Sci, 2014; 6(2):69–80. CrossRef

Reference

Abouzeed YM, Zgheel F, Elfahem AA, Almagarhe MS, Dhawi A, Elbaz A, Hiblu MA, Kammon A, Ahmed MO. Identification of phenolic compounds, antibacterial and antioxidant activities of raisin extracts. Open Vet J, 2018; 8(4):479-84. https://doi.org/10.4314/ovj.v8i4.20

Ahmad Al, Ahmad E, Rabbani G, Haque S, Arshad M, Khan RH. Identification and design of antimicrobial peptides for therapeutic applications. Curr Protein Pept Sci, 2012; 13(3):211-23. https://doi.org/10.2174/138920312800785076

Alam M, Ali R, Marella A, Alam T, Naz R, Akhter M, Shaquiquzzaman M, Saha R, Tanwar O, Hooda J. Review of biological activities of hydrazones. Indonesian J Pharm, 2012; 23(4):193-202.

Bala S, Uppal G, Kajal A, Kamboj S, Sharma V. Hydrazones as promising lead with diversity in bioactivity-therapeutic potential in present scenario. Int J Pharm Sci Rev Res, 2013; 18(1):65-74.

Bala S, Uppal G, Kamboj S, Saini M. Therapeutic review exploring antimicrobial potential of hydrazones as promising lead. Der Pharma Chemica, 2011; 3(1):250-68.

Bala S, Uppal G, Kamboj S, Saini V, Prasad DN. Design, characterization, computational studies and pharmacological evaluation of substituted-N′-[(1E) substituted phenylmethylidene] benzohydrazide analogs. Med Chem Res, 2012; 21(11):1-13. https://doi.org/10.1007/s00044-012-0270-0

Benslama A, Harrar A, Gul F, Demirtas I. Phenolic compounds, antioxidant and antibacterial activities of Zizyphus lotus L. leaves extracts. Nat Prod J, 2017; 7(4): 316-22. https://doi.org/10.2174/2210315507666170530090957

Cappucino JG, Sherman N. Microbiology-a laboratory manual. Addison Wesley, Redwood City, CA, 1999.

Chaudhary J, Rajpal AK, Judge V, Narang R, Narasimhan B. Preservative evaluation of caprylic acid derivatives in aluminium hydroxide gel-USP. Sci Pharm, 2008;76(3):533-40. https://doi.org/10.3797/scipharm.0807-24

Dudhe R, Sharma PK, Dudhe AC, Verma PK. Synthesis and antioxidant activities of 6- Aryl-3,4-dihydro-1-(tetrahydro-3,4-Dihydroxy- 5-(hydroxymethyl)-furan-2-yl)-4-phenyl-pyrimidine- 2(1H)-thione derivatives. Eur Chem Bull, 2013; 2(6):341-47.

Emami S, Foroumadi A, Falahati M, Lotfali E, Rajabalian S, Ebrahimi A, Farahyar S, Shafiee A. 2-Hydroxyphenacyl azoles and related azolium derivatives as antifungal agents. Bioorg Med Chem, 2008; 18:141-6. https://doi.org/10.1016/j.bmcl.2007.10.111

Fu L, Lu WQ, Zhou XM. Phenolic compounds and in-vitro antibacterial and antioxidant activities of three tropic fruits: persimmon, guava and sweetsop. Biomed Res Int, 2016; 2016:9. https://doi.org/10.1155/2016/4287461

Hadi A, Alireza F, Reza K, Karim N, Mostafa RT. Synthesis and investigation of antioxidant activities of 2-benzylidene-3-coumaranones. J Paramed Sci, 2013; 4(2):76-81.

Halliwell B, Aerchabach R, Lologer J, Aruoma OI. The characterization of antioxidants. Food Chem Toxicol, 1995; 33(7):601-17. https://doi.org/10.1016/0278-6915(95)00024-V

Harer SL, Rajurkar VG, Patil P, Harer PS, Navale SD, Awuti ST, Sonawane AA. Synthesis, characterization and anti-microbial evaluation of some 2- iodo-N'-[(1E)-substituted phenylmethylidene] benzohydrazide analogues. IJPSDR, 2010; 2(2):134-6.

Hossain MM, Shaha SK, Aziz F. Antioxidant potential study of some synthesized N-heterocycles. Bangladesh Med Res Counc Bull, 2009; 35:49-52. https://doi.org/10.3329/bmrcb.v35i2.2564

Kapoor A, Dahiya SK. Synthesis and evaluation of 2-aryl substituted benzimidazole derivatives bearing 1,3,4-oxadiazole nucleus for antimicrobial activity. Der Pharmacia Lettre, 2016; 8(12):57-67.

Khatkar A, Nanda A, Kumar P, Narasimhan B. Synthesis, antimicrobial evaluation and QSAR studies of p-coumaric acid derivatives. Arab J Chem, 2017; 10(2):S3804-15. https://doi.org/10.1016/j.arabjc.2014.05.018

Kumar NA, Chauhan LS. Analgesic and anti-inflammatory potential of hydrazones. J Chem Pharm Res, 2014;6(12):916-34.

Lindahl JF, Grace D. The consequences of human actions on risks for infectious diseases: a review. Infect Ecol Epidemiol, 2015; 5(10):3402. https://doi.org/10.3402/iee.v5.30048

Makki MST, Rahman RMA, Ali OAA. Synthesis of new fluorinated 1,2,4-triazino [3,4-b][1,3,4]thiadiazolones as antiviral probes-part II- reactivities of fluorinated 3-aminophenyl-1,2,4- triazinothiadiazolone. Int J Org Chem, 2015; 5(3):1-12. https://doi.org/10.4236/ijoc.2015.53017

Manuja R, Sachdeva S, Jain A, Chaudhary J. A comprehensive review on biological activities of p-hydroxy benzoic acid and its derivatives. Int J Pharm Sci Rev Res, 2013; 22(2):109-115.

Marwa AM, Ahmed N. Biological activity of some newly synthesized hydrazone derivatives derived from (dicyclopropylmethylene) hydrazone. Eur Chem Bull, 2018; 7(10):280-7. https://doi.org/10.17628/ecb.2018.7.280-287

Narang R, Narasimhan B, Sharma S. Synthesis, antimycobacterial, antiviral, antimicrobial activities, and QSAR studies of nicotinic acid benzylidene hydrazide derivatives. Med Chem Res, 2012; 21(9):2526-47. https://doi.org/10.1007/s00044-011-9776-0

Neda OA, Denista YY, Anelia TM, Magdalena SKB, Virginia IT, Nadya GHA,Vera AH. Design, synthesis, antioxidant properties and mechanism of action of new N,N′-disubstituted benzimidazole-2-thione hydrazone derivatives. J Mol Struct, 2018; 1165:162-76. https://doi.org/10.1016/j.molstruc.2018.03.119

Nurkenov OA, Satpaeva B, Schepetkin IA, Khlebnikov AI, Turdybekov KM, Seilkhanov TM, Fazylov SD. Synthesis and biological activity of hydrazones of o- and p-hydroxybenzoic acids. Spatial structure of 5-Bromo-2-hydroxybenzylidene-4-hydroxybenzohydrazide. Russ J Gen Chem, 2017; 87(10):2299-306. https://doi.org/10.1134/S1070363217100097

Pontiki E, Litina DH. Multi-target cinnamic acids for oxidative stress and inflammation: design, synthesis, biological evaluation and modeling studies. Molecules, 2019; 24(1):12. https://doi.org/10.3390/molecules24010012

Popiolek L. Hydrazide-hydrazones as potential antimicrobial agents: overview of the literature since 2010. Med Chem Res, 2017; 26(2):287-301. https://doi.org/10.1007/s00044-016-1756-y

Rajput AP, Rajput SS. Synthesis of benzaldehyde substituted phenyl carbonyl hydrazones and their formylation using Vilsmeier-Haack reaction. Int J PharmTech Res, 2009; 1(4):1605-11.

Rayam P, Anireddy JS, Polkama N, Allakaa TR, Chepurib K, Mukharjee N. Synthesis and biological activity of novel acyl hydrazone derivatives of 3-(4,5-diphenyl1,3-oxazol-2-yl) propanoic acid as anticancer, analgesic and anti-inflammatory agents. J Paramed Sci, 2015; 9(2):157-64.

Ruch RJ, Cheng SJ, Klannig JE. Prevention of cytotoxicity and inhibition of intercellular communication by antioxidant catechins isolated from Chinese green tea. Carcinogensis, 1989; 10:1003-8. https://doi.org/10.1093/carcin/10.6.1003

Sapra A, Kumar P, Kakkar S, Narasimhan B. Synthesis, antimicrobial evaluation and QSAR studies of p -hydroxy benzoic acid derivatives. Drug Res, 2014; 64:17-22. https://doi.org/10.1055/s-0033-1349866

Shukla S, Mehta A, John J, Singh S, Mehta P, Vyas SP. Antioxidant activity and total phenolic content of ethanolic extract of Caesalpinia bonducella seeds. Food Chem Toxicol, 2009; 47:1848-51. https://doi.org/10.1016/j.fct.2009.04.040

Singh N, Ranjana R, Kumari M, Kumar M. A review on biological activities of hydrazone derivatives. Int J Pharm Clin Res, 2016; 8(3):162-6.

Soares JR, Dinis TCP, Cunha AP, Almeida LM. Antioxidant activities of some extracts of Thymus zygis. Free Radic Res, 1977; 26: 469-78. https://doi.org/10.3109/10715769709084484

Sortino M, Garibotto F, Cechinel FV, Gupta M, Enriz R, Zacchino S. Antifungal, cytotoxic and SAR studies of a series of N-alkyl, N-aryl and N-alkylphenyl-1,4-pyrrolediones and related compounds. Bioorg Med Chem, 2011; 19(9):2823-34. https://doi.org/10.1016/j.bmc.2011.03.038

Sprong RCA, Winkelhuyzen JC, Aarsman J, van Oirschot T, Vandeer B, VanAsbeck B. Low dose N-acetylcysteine protects rats against endotoxin mediated oxidative stress, but high dose increases mortality. Am J Respir Crit Care Med, 1998; 157: 1283-93. https://doi.org/10.1164/ajrccm.157.4.9508063

Suzana I, Tutuk B. Synthesis, molecular docking and antimicrobial of N'-benzylidene-4-hydroxybenzohydrazide and N'- (4-methoxybenzylidene)-4-hydroxybenzohydrazide. RJPBS, 2017; 8(2):1354-61.

Velika B, Kron I. Antioxidant properties of benzoic acid derivatives against superoxide radical. Free Radical and Antioxidants. 2012; 2(4):62-7. https://doi.org/10.5530/ax.2012.4.11

Venkatesh T, Bodke YD, Kenchappa R, Telkar S. Synthesis, antimicrobial and antioxidant activity of chalcone derivatives containing thiobarbitone nucleus. Med Chem, 2016; 6: 440-8. https://doi.org/10.4172/2161-0444.1000383

Verma G, Marella A, Shaquiquzzaman M, Akhtar M, Ali MR, Alam MM. A review exploring biological activities of hydrazones. J Pharm Bioallied Sci, 2014; 6(2):69-80. https://doi.org/10.4103/0975-7406.129170

Article Metrics

636 Absract views 119 PDF Downloads 755 Total views

   Abstract      Pdf Download

Related Search

By author names

Citiaion Alert By Google Scholar

Name Required
Email Required Invalid Email Address

Comment required