Salicylaldehyde Schiff bases Bioactivity Prediction by Insilico Approach

Valli G., Ramu K., Mareeswari P.

Department of Chemistry, SFR College for women, Sivakasi.

*Corresponding Author E-mail: Mrs.Valliravichandran@gmail.com

ABSTRACT:

Our study focuses the prediction of the bioactivity of Salicylaldehyde Schiff bases by computational method using PASS (online software for bioactivity prediction) by knowing the importance of Schiff bases derived from salicylaldehyde with various amines. Thirteen Schiff bases selected for our work. PASS prediction result showed that salicylaldehyde o-phenylenediamine Schiff bases possessed higher laccase inhibitor (91.6% )activity and 3-hydroxybenzoate 4-monooxygenase inhibitor(88%) activities. salicylaldehyde luicine Schiff base possessed antiseborrheic(86.1%), Pro-opio melanocortin converting enzyme inhibitor(86.5%) and protein-glutamate methyl esterase activity(85.2%). salicylaldehyde Schiff bases derived from 2-aminopyridine, ethylenediamine, Glycine, 2,4-dinitrophenylhydrazine, 4-aminobenzene sulphonamide and methionine were found to have Glutathione thiolesterase inhibitor(86.3%), Glucose oxidase inhibitor (86.1%), Monophenol monooxygenase inhibitor (86.5%) , Cis-1,2-dihydro-1,2dihydroxy naphthalene dehydrogenase inhibitor (89.5%),Anthranilate 3-monooxygenase (deaminating)Inhibitor(88.7%) ,Corticosteroid side-chain-isomerase inhibitor (88.7%), Sulfite reductase inhibitor(86.1%), Pullulanase inhibitor (85.8%) and 3-Phytase inhibitor(85.4%). Aryl acetonitrilase inhibitor (85.2%), Arylformamidase inhibitor (91.2%), Phenylalanine (histidine) transaminase inhibitor (89.4%) and L-3-cyanoalanine synthase inhibitor (88.9%) activities. They also found to act as Dopamine D4 agonist (89.5%) and Antiprotozoal (Toxoplasma) (87%) compared to other Schiff bases.

KEYWORDS: o-phenylenediamine, Luicine, Laccase , salicylaldehyde, PASS.

INTRODUCTION:

The Schiff bases find use in analytical chemistry, agriculture, dyes and polymer industries besides their utility as model systems in the field of bio-inorganic chemistry. Schiff bases serve as useful gravimetric, colorimetric agents and as a regulant and as well as anti-coagulant, the oxygen carrying property, electron transfer reactions of various schiff bases have been reported.

Schiff bases exhibit good antimicrobial activity and finds its applications in pharmacology [1]. These compounds showed good fungicidal activity and anti-inflammatory activities. Number of formazans have been claimed to possess promising antifertility[2] and antiviral activities particularly against ranikhet disease virus and plant virus. Recently, Jolly et. al. have synthesized new formazans for assessing their antiviral, anticancer and anti HIV activities[3]. Schiff bases are frequently studied due to optical, catalytic, chromophoric, thermo chromic, and photo chromic properties.

Various Schiff bases derived from salicylaldehyde 2-aminophenol and 2,4-dinitrophenylhydrazine have shown strong cytotoxic effect towards brine shrimp naupli.[4]. salicylaldehyde and o-pheneylenediamine schiff bases exhibit bacterial activity on some pathogenic bacteria [5] and also employed in analytical studies. Salicylaldehyde Schiff bases of various amino acid like glycine, phenylalanine, methionine were found to have radio protective, antibacterial, fungi static [6,7], DNA cleavable [8], antipyretic, antidiabetic activities[9].

Knowing the importance of salicylaldehyde schiff bases derived from Salicylaldehyde from various literature sources, We plan to predict the bioactivity of some of the schiff bases of salicylaldehyde using online software. PASS (Prediction of Activity Spectra for Substances) Thirteen selected Schiff bases of Salicylaldehyde were predicted by PASS prediction.

Insilico prediction of biological activity using PASS in relation to the chemical structure of a compound is now a commonly used technique in drug discovery and development to predict the biological activity spectrum for a compound on the basis of its structural formula. It helps in finding most probable new leads with required activity spectra among the compounds from in-house and commercial data bases [10-14]. PASS is a software product designed as a tool for evaluating the general biological potential of an organic drug-like molecule. PASS provides simultaneous prediction of many types of biological activity based on the structure of organic compounds. It can predict more than 1500 pharmacological effects, molecular mechanism of action and toxicities on basis of structural descriptors of compounds. Thus PASS can be used to estimate the biological activity profiles for virtual molecules, prior to their chemical synthesis and biological testing.

Pa (Prabability to be active) estimates the chance that the studied compound is belonging to the sub-class of active compounds resembles the structures of molecules, which are the most typical in a sub-set of actives in PASS training set.

Pi (probability to be inactive) estimates the chance that the studied compound is belonging to the sub-class of inactive compounds resembles the structures of molecules, which are the most typical in a sub-set of inactives in PASS training set.

MATERIALS AND METHODS:

Materials

Schiff bases derived from salicylaldehyde and amines like 2-aminopyridine, Ethylenediamine, Glycine, Luicine, 3-chloroaniline, O-phenylenediamine, 2,4-dinitro phenylhydrazine, O-Toluidine, L-Pheny alanine,

4-Aminobenzene sulphonamide, Methionine, 2-Aminophenol, 2-Aminobenzaldehyde were selected for our studies.

Various Schiff bases (1a-1m) given below were choosen.

Ia Ib

N-(2hydroxybenzylidine) pyridine-2-amine 2-(2-aminoethylimino) methyl) phenol

2-(2-hydroxybenzylideneamino) acetic acid Id

2-(2-hydroxybenzylideneamino)-4-methylpentanoic acid

Ie If

2-((3-chlorophenylimino)methyl)phenol 2-((2-aminophenylimino)methyl)phenol

Ig Ih

2-((2-(2,4-dinitrophenyl)hydrazono)methyl)phenol 2-((o-tolylimino)methyl)phenol

2-(2-hydroxybenzylidineamino) phenol Ij

2-(2-hydroxybenzylidineamino) phenol

Ik Il

2-(2-hydroxybenzylideneamino)-4-(methylthio)butanoic acid 2-(2-hydroxybenzylideneamino)-3-phenylpropanoicacid

2-(2-hydroxybenzylidneamine) phenol

Methods

Chemdraw ultra11.0 software

The structure of schiff bases listed (Ia-Im) were drawn in chemultra11.0 appeared was given in Fig.1. and their structures were saved as molfiles(*.mol).

Fig.1. Structure of 2-(pyridin-2-ylimino)methyl)phenol

Docking

The possible bioactivities of all the molecules were predicted with PASS software (V.Poroikov et al, version 1.917).

Opening the PASS software the window appears as given in Fig.2.

Fig.2. PASS Prediction window

PASS Predictions bioactivity result of the selected compound appear on the new window as given in Fig.3.

Fig.3. PASS Prediction of -2-(pyridin-2-ylimino)methyl)phenol

Table -1.PASS Prediction activities of Salicylaldehyde Schiff bases:

S.NO	Activity	Compound	Pa	Pi
1.	Laccase inhibitor	2-(2-hydroxybenzylidineamino)phenol 2-((2-aminophenylimino)methyl)phenol 2-(2-hydroxybenzylideneamino)-4-methylpentanoic acid 2-((o-tolylimino)methyl)phenol 2-((3-chlorophenylimino)methyl)phenol 2-(2-aminoethylimino)methyl)phenol	0.916 0.915 0.907 0.876 0.856 0.853	0.004 0.004 0.004 0.006 0.009 0.009
2.	Glutathione thiolesterase inhibitor	2-(pyridin-2-ylimino)methyl)phenol	0.863	0.007
3.	Glucose oxidase inhibitor	2-(2-aminoethylimino)methyl)phenol	0.861	0.016
4.	Monophenol monooxygenase inhibitor	2-(2-hydroxybenzylideneamino)-4-methylpentanoic acid 2-(2-hydroxybenzylideneamino)-3-phenylpropanoicacid 2-(2-hydroxybenzylidineamino)phenol	0.895 0.893 0.854	0.004 0.004 0.004
5.	3-Hydroxybenzoate 4-monooxygenase inhibitor	2-((2aminophenylimino)methyl)phenol 2-(2-hydroxybenzylidineamino)phenol	0.880 0.859	0.003 0.003
6.	Pro-opiomelanocortin converting enzyme inhibitor	2-(2-hydroxybenzylideneamino) acetic acid	0.865	0.018
7.	Antiseborrheic	2-(2-hydroxybenzylideneamino) acetic acid	0.861	0.018
8.	Protein-glutamate methylesteraseinhibitor	2-(2-hydroxybenzylideneamino) acetic acid	0.852	0.018

Table-II. PASS Prediction activities of Salicylaldehyde Schiff bases

S.NO	Activity	Compound	Pa	Pi
9.	Cis-1,2-dihydro-1,2d ihydroxynaphthalenedehydrogenaseinhibitor	2-(2-hydroxybenzylideneamino)-4-methylpentanoic acid	0.895	0.003
10	Anthranilate 3-monooxygenase (deaminating) Inhibitor	2-(2-hydroxybenzylideneamino) 4-methylpentanoic acid	0.887	0.002
11.	Corticosteroid side-chain-isomeraseinhibitor	2-(2-hydroxybenzylideneamino)-4-methylpentanoic acid	0.880	0.004
12.	Sulfite reductase inhibitor	2-(2-hydroxybenzylideneamino)-4-methylpentanoic acid	0.861	0.004
13.	Pullulanase inhibitor	2-(2-hydroxybenzylideneamino)-4-methylpentanoic acid	0.858	0.013
14.	3-Phytase inhibitor	2-(2-hydroxybenzylideneamino)-4-methylpentanoic acid	0.854	0.005
15.	Arylacetonitrilase inhibitor	2-((2-(2,4dinitrophenyl)hydrazono)methyl)phenol	0.852	0.020
16.	Dopami D4 agonist	2-(2-hydroxybenzylidineamino)phenol	0.895	0.004
17.	Antiprotozoal (Toxoplasma	2-(2-hydroxybenzylidineamino)phenol	0.870	0.009
18.	Arylformamidase inhibitor	2-(2-hydroxybenzylideneamino)-4-(methylthio)butanoic acid	0.912	0.002
19.	Phenylalanine(histidine) transaminase inhibitor	2-(2-hydroxybenzylideneamino)-4-(methylthio)butanoic acid	0.894	0.003
20.	L-3-cyanoalanine synthase inhibitor	2-(2-hydroxybenzylideneamino)-4-(methylthio)butanoic acid	0.889	0.002

Laccase inhibitor activity

The Laccase inhibitor activity of the schiff bases such as 2-(2-hydroxybenzylidineamino)phenol(Pa=0.916), 2-((2-aminophenylimino)methyl)phenol (Pa=0.915), 2-(2-hydroxybenzylideneamino)-4-methylpentanoic acid (Pa=0.907), 2-((o-tolylimino)methyl)phenol (Pa=0.876),2-(2-hydroxy benzylidine amino)phenol,(Pa=0.865), 2-((3-chlorophenylimino) methyl)phenol (Pa=0.856), 2-(2-amino ethylimino)methyl)phenol (Pa=0.853), were found to possess greater than 80 % of activities

Glucose oxidase inhibitor

Glucose oxidase diagnose diabetes by determining whether glucose is present in the patient's urine and used to estimate glucose concentration in blood or urine samples. Glucose oxidase inhibitor activity was observed for 2-(2-aminoethylimino)methyl)phenol whose Pa was 86.1%.

Monophenol monooxygenase inhibitor

Monophenol monooxygenase inhibitor activity of 2-(2-hydroxybenzylideneamino)-4-methylpentanoic acid was found to be 89.5 %.

3-Hydroxybenzoate 4-monooxygenase inhibitor

3-Hydroxybenzoate 4-monooxygenase inhibitor activity of the compound Id & If were found to be greater than 85% of activity.

Pro-opiomelanocortin converting enzyme inhibitor Activity

2-(2-hydroxybenzylideneamino) acetic acid showed (Pa = 0.865) for Pro-opiomelanocortin converting enzyme inhibitor activity.

Antiseborrheic Activity

Antiseborrheic is a substance that controls the excessive secretion of serum and reduces oiliness of the face and greasy scalp, a condition that is most common in adolescents. Antiseborrheic activity of 2-(2-hydroxybenzylideneamino) acetic acid was observed to be 0.861 Pa value.

Protein-glutamate methylesterase inhibitor

2-(2-hydroxybenzylideneamino) acetic acid was found to possess Protein-glutamate methylesterase inhibitor with Pa value of 85% of activity.

Corticosteroid side-chain-isomerase inhibitor

Corticosteroid side-chain-isomerase inhibitor activity was observed in -2-(2-hydroxybenzylideneamino)-4-methylpentanoic acid (88%) given in Table-II.

Arylacetonitrilase inhibitor

2-((2-(2,4dinitrophenyl)hydrazono)methyl)phenol can exhibit Arylacetonitrilase inhibitor activity (Pa=0.854)

Dopamine D4 agonist

Dopamine D4 agonist activity was observed by 2-(2-hydroxybenzylidineamino)phenol in 89.5% of activity.

Antiprotozoal

Antiprotozoal are used to treat malarial disease. Antiprotozoal activity of 2-(2-hydroxybenzylidineamino) phenol was found to be 87% of activity.

Arylformamidase inhibitor

Arylformamidase inhibitor activity of 2-(2-hydroxybenzylideneamino)-4-(methylthio)butanoic acid was 91.2% of activity.

DISCUSSION:

PASS prediction bioactivity of the salicylaldehyde schiff bases were given in the Table-I & II. We observed the following result.

For the Laccase inhibitor activity Pa value ranges from 0.916-0.853. Among compound If, Id, Ih, Ie, Ib, Im have highest laccase inhibitor activity of 91.6% of activity.

Monophenol monooxygenase inhibitor activity of 2-(2-hydroxybenzylideneamino)-4-methylpentanoic acid was higher than other schiff bases.

Cis-1,2-dihydro-1,2dihydroxynaphthalenedehydrogenaseinhibitor, Anthranilate 3-monooxygenase (deaminating) Inhibitor, Corticosteroid side-chain-isomerase inhibitor, Sulfite reductase inhibitor, Pullulanase inhibitor and 3-Phytase inhibitor activities were observed by 2-(2-hydroxybenzylideneamino)-4-methylpentanoic acid. 2-(pyridin-2-ylimino)methyl) phenol was found to have Glutathione thiolesterase inhibitor activity, 2-(2-aminoethylimino)methyl)phenol exhibit Glucose oxidase inhibitor activity, 2-(2-hydroxybenzylideneamino) acetic acid showed Pro-opiomelanocortin converting enzyme inhibitor activity, antiseborrheic, protein-glutamate methylesterase activities. 2-((2-(2,4-dinitrophenyl)hydrazone)methyl)phenol was found to possess Arylacetonitrilase inhibitor activity 2-(2-hydroxybenzylideneamino)-4-(methylthio)butanoic acid have shown to be Arylformamidase inhibitor and L-3-cyanoalanine synthase inhibitor .

CONCLUSION:

Among all the thirteen schiff bases selected for our work. (2-hydroxybenzylidineamino)phenol have the highest laccase inhibitor activity (91.2%). 2-(2-hydroxybenzylideneamino)-4-methylpentanoic acid was found to possessed highest Monophenol monooxygenase inhibitor (89.5%) and also exhibit Corticosteroid side-chain-isomerase inhibitor. Pullulanase inhibitor and 3-Phytase inhibitor activities. 2-((2-aminophenylimino) methyl) phenol showed to be 3-Hydroxybenzoate 4-monooxygenase inhibitor activity (88%). Therefore we conclude that (2-hydroxybenzylidineamino)phenol may be used as a good alternative for laccase inhibitor.

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Received on 09.02.2012 Modified on 25.02.2012

Asian J. Research Chem. 5(4): April 2012; Page 504-509