Order Molecular Connectivity Index Research Articles

Synthesis, Biological Evaluation, QSAR, Molecular Docking and ADMET Studies of N-aryl/N,N-dimethyl Substituted Sulphonamide Derivatives

<P>Background: Rapid evolution of drug resistance and side effects of currently used drugs develop more efficacious and newer antimicrobial agents. Further, for the management of Type II Diabetes, α-gulcosidase and α-amylase inhibitors play a very important role by inhibiting the postprandial hyperglycemia. </P><P> Objectives: The objective of this study was to synthesize N-aryl/N,N-dimethyl sulphonamides, investigate their antihyperglycemic and antimicrobial potential, develop QSAR model for identifying molecular descriptors and predict their binding modes and in silico ADMET properties. </P><P> Methods: Synthesized derivatives were subjected to in vitro studies for their antidiabetic activity against α-glucosidase and α-amylase enzymes and antimicrobial activity. Molecular docking studies were carried out to find out molecular binding interactions of the ligand molecules with their respective targets. QSAR studies were carried out to identify structural determinants responsible for antimicrobial activity. </P><P> Results: Antidiabetic study demonstrated the potent activity of two compounds 2 and 6 as α- glucosidase and α-amylase inhibitors, as well as compound 1 and 2, exhibited potent antimicrobial activity against all the tested microbes. All the compounds have more antifungal potential against Candida albicans. QSAR studies confirmed the role of molecular connectivity indices (valence first order and second order) in controlling the antimicrobial activity. Molecular docking studies supported the observed in vitro biological activities of the synthesized compounds. </P><P> Conclusion: The compounds with 2,3-dimethyl substitution were found to be antidiabetic agents and molecules having bromo and 2,3-dimethyl substituents on phenyl ring have established themselves as potent antimicrobial agents. The role of valence first and 2nd order molecular connectivity indices as molecular properties were identified for antimicrobial activity and various electrostatic, hydrogen bonding and hydrophobic interactions were found to be prominent in the binding of molecules at the target site.</P>

Synthesis, antimicrobial, anticancer and QSAR studies of 1-[4-(substituted phenyl)-2-(substituted phenyl azomethyl)-benzo[b]-[1,4]diazepin-1-yl]-2-substituted phenylaminoethanones

A series of 1-[4-(substituted phenyl)-2-(substituted phenyl azomethyl)-benzo[b]-[1,4]diazepin-1-yl]-2-substituted phenylaminoethanones (1–17) was synthesized and evaluated in vitro for its antimicrobial and anticancer activities. Results of antimicrobial screening indicated that 1-[4-[4-Chloro-phenyl)-2-[(3-nitro-phenylazo)-methyl]-benzo[b][1,4]diazepin-1-yl]-2-(2-methyl-5-nitro-phenyl amino)-ethanone (16) and 1-[4-(3,4-dimethoxy-phenyl)-2-[(4-nitro-phenylazo)-methyl]-benzo[b][1,4]diazepin-1-yl]-2-(3-nitrophenylamino)-ethanone (17) were found to be the most effective antimicrobial agents. The anticancer screening results indicated that 1-[4-(4-dimethylamino-phenyl)-2-(p-tolylazo-methyl)-benzo[b][1,4]diazepin-1-yl]-2-phenyl aminoethanone (1, IC50=1.42μM/mL against HCT 116 cancer cell lines) was the most potent anticancer agent and was more potent than 5-FU. The results of QSAR studies demonstrated the importance of topological parameters, Kier’s alpha first order shape index (κα1) and valence zero order molecular connectivity index (0χv) in describing antimicrobial activity, LUMO and κα2 in describing anticancer activity of 1-[4-(substituted phenyl)-2-(substituted phenyl azomethyl)-benzo[b]-[1,4]diazepin-1-yl]-2-substituted phenylaminoethanones.

Synthesis, antimicrobial, anticancer evaluation of 2-(aryl)-4- thiazolidinone derivatives and their QSAR studies.

A new class of 4-thiazolidinones clubbed with quinozolinone nucleus has been synthesized. The title compounds were screened for their in vitro antimicrobial and anticancer potentials. Results of antimicrobial and anticancer study revealed that compounds 7 (pMICam = 1.69 μM/ml) and 2 (IC50 = 12.83 μM) were found to be the most potent antimicrobial and anticancer agents respectively. QSAR studies indicated that antimicrobial activity of synthesized 4-thiazolidinone derivatives was governed by the electronic parameters, dipole moment (μ), energy of highest occupied molecular orbital (HOMO), lipophilic parameter, log P and topological parameter, valence third order molecular connectivity index ((3)χ(v)).

Synthesis, antimicrobial, anticancer evaluation and QSAR studies of 3/4-bromo benzohydrazide derivatives.

A series 3/4-bromo-N'-(substituted benzylidene/furan-2-ylmethylene/5-oxopentylidene/3- phenylallylidene)benzohydrazides (1-23) was synthesized and characterized by physicochemical and spectral means. The synthesized compounds were screened for their antimicrobial and anticancer potentials. Antimicrobial activity results indicated that compound 12 (pMICam = 1.67 μM/ml) was the most potent antimicrobial agent. The synthesized benzohydrazides were also having good anticancer potential and compound 22 (IC50 = 1.20 μM μM) was found to be the most potent anticancer agent which was more potent than standard drugs, tetrandrine (IC50 = 1.53) and 5- fluorouracil (IC50 = 4.6 μM). QSAR studies indicated that antimicrobial activity of synthesized compounds was best described by electronic parameter, total energy (Te) and topological parameters, valance zero order molecular connectivity index ((0)χ(v)) and Wiener index (W).

Synthesis, antimicrobial evaluation and QSAR studies of p-coumaric acid derivatives

A series of p-coumaric acid derivatives (1–36) was synthesized and characterized by physicochemical as well as spectral means. The synthesized compounds were evaluated in vitro for their antimicrobial activity against different Gram positive and Gram negative bacterial and fungal strains by the tube dilution method. Results of antimicrobial screening indicated that compound 17 was the most active antimicrobial agent (pMICam=1.73μM/mL). The results of QSAR studies demonstrated that antibacterial, antifungal and overall antimicrobial activities of synthesized p-coumaric acid derivatives were governed by the electronic parameter, electronic energy (Ee) and topological parameters first order molecular connectivity index (1χ) and Wiener index (W).

Synthesis, antimicrobial, anticancer evaluation and QSAR studies of 2/3-bromo-N′-(substituted benzylidene/3-phenylallylidene)benzohydrazides

In the present study, a series of 2/3-bromo-N′-(substituted benzylidene/3-phenylallylidene)benzohydrazides was synthesized and evaluated in vitro for its antimicrobial and anticancer potentials. The results of antimicrobial and anticancer study indicated that compounds 3, 15 and 18 (pMICam=1.62μM/ml) were found to be most potent antimicrobial agents and compound 4 (IC50=1.88±0.03μM) was found to be the most potent anticancer agent. The results of QSAR analysis indicated the importance of topological parameters, Balaban index (J) and valence first and second order molecular connectivity indices (1χv and 2χv) in describing antimicrobial activity of the synthesized benzohydrazides.

Predictive modeling of chemical toxicity towards Pseudokirchneriella subcapitata using regression and classification based approaches

Biodiversity nurturing may be a valuable pathway in controlling chemical stress on the ecosystem. In the present work, in silico studies have been performed to develop regression based quantitative structure toxicity relationship (QSTR) models using a data set containing 105 organic chemicals for the prediction of 48-h chemical toxicity towards Pseudokirchneriella subcapitata. Classification based linear discriminant analysis (LDA) was also performed to distinguish chemicals into toxic and nontoxic groups using the same data set. The developed models were found to possess good predictive quality in terms of internal, external and overall validation parameters. The regression based QSTR model suggests that second order molecular connectivity index (molecular size and lipophilicity), density (aromaticity), relative shape of molecules (cyclicity/aromaticity), and specific molecular fragments of the chemicals are important properties of chemicals to exert their toxicity on P. subcapitata. The classification based LDA QSTR model suggested that fused ring aromatic systems, secondary carbon atom fragments, second order valence molecular connectivity indices (molecular size and branching) and molecular weight are the distinguishing features to differentiate chemicals into toxic and nontoxic groups.

Synthesis, Antimicrobial Evaluation and QSAR Studies of 2-chlorobenzoic Acid Derivatives

In the present study, 2-chlorobenzoic acid derivatives were synthesized and evaluated for their antimicrobial activity against Gram-positive bacteria: Staphylococcus aureus, Bascillus subtilis, Gram-negative bacterium Escherichia coli, fungal strains: Candida albicans and Aspergillus niger by tube dilution method. Results of antimicrobial screening indicated that the synthesized compounds exhibited greater antibacterial potential against Gram-negative bacterium (Escherichia coli) than Gram-positive bacteria and the Schiff's bases of 2-chloro benzoic acid were more potent antimicrobial agents than its esters. Compound 6 (pMIC(am)=1.91 µM/ml, pMIC(ec)=2.27 µM/ml) emerged as most potent antimicrobial agent and was found comparable to standard drug norfloxacin (pMIC(ec)=2.61 µM/ml) against Escherichia coli. QSAR studies revealed that the antibacterial, antifungal and the overall antimicrobial activities of the 2-chlorobenzoic acid derivatives were governed by the topological parameters, second order and valence second order molecular connectivity indices ((2)χ and (2)χ(v)).

Synthesis, Antimicrobial Evaluation and QSAR Studies of 2-hydroxy Propanoic Acid Derivatives

A series of 2-hydroxypropanoic acid derivatives (1-26) was synthesized and characterized by physicochemical and spectral means. The synthesized compounds were evaluated for their in vitro antimicrobial potential and the results indicated that compounds 5 and 12 were found to be the most potent antimicrobial agents having pMICam values 1.67 and 1.64 µM/ml respectively. QSAR studies indicated the importance of topological parameter, Kier's valance second order molecular connectivity index (2χv) in describing the antimicrobial activities of synthesized 2-hydroxypropanoic acid derivatives.

Synthesis, Antimicrobial, Anticancer Evaluation and QSAR Studies of Thiazolidin-4-Ones Clubbed with Quinazolinone

A series of 3-(5-(arylidene)-2-(aryl)-4-oxothiazolidin-3-yl)-2-phenylquinazolin-4(3H)-one derivatives (1-18) was synthesized in appreciable yield and characterized by physicochemical and spectral means. The synthesized compounds were evaluated for their in vitro antimicrobial and anticancer potentials. Antimicrobial properties of the title compounds were investigated against Gram positive and Gram negative bacterial as well fungal strains. 3-(5-(3- Methoxybenzylidene)-2-(4-(dimethylamino)phenyl)-4-oxothiazolidin-3-yl)-2-phenyl quinazolin-4(3H)-one (16, pMICam = 1.71 µM/ml) was found to be the most active antimicrobial agent. The anticancer evaluation of synthesized compounds against human colon (HCT116) cancer cell line indicated that 3-(5-(4-bromobenzylidene)-2-(3-chlorophenyl)-4- oxothiazolidin-3-yl)-2-phenylquinazolin-4(3H)-one (7, IC50 = 5.27 µM) was the most active anticancer agent and was more potent than standard drug, 5-fluorouracil (IC50 = 6.00 µM). QSAR models developed for antimicrobial activity of synthesized compounds indicated that antimicrobial activity of synthesized 4-thiazolidinone derivatives was governed by the topological parameters, valence first and second order molecular connectivity indices ((1)Χ(v) and (2)Χ(v)) and the electronic parameters, total energy (Te) and cosmic energy (Cos E).

Synthesis, Antimicrobial Evaluation and QSAR Studies of p-hydroxy Benzoic Acid Derivatives

In the present study, a series of p-hydroxy benzoic acid derivatives (1-29) was synthesized and tested for its antimicrobial potential. Results of antimicrobial studies indicated that in general, Schiff bases were found to be more active as compared to esters and compound 14 was found to be most potent antimicrobial agent (pMICam=1.50 µM/ml). QSAR study was performed in order to understand the relationship between antimicrobial activity and changes in the molecular structures which indicated that antimicrobial activity of the synthesized compounds was governed by valence first order molecular connectivity index (1χv), Kier's alpha first order shape index (κα1), Kier's first order shape index (κ1) and Balaban topological index (J).

Synthesis, antimicrobial, anticancer evaluation and QSAR studies of N′-substituted benzylidene/2-hydroxynaphthalen-1-ylmethylene/3-phenylallylidene/5-oxopentylidene -4-(2-oxo-2-(4H-1,2,4-triazol-4-yl) methylamino)benzohydrazides

A series of 1,2,4-triazole derivatives (1–17) was synthesized and evaluated for its antimicrobial and anticancer potentials. Antimicrobial screening of the synthesized compounds indicated that they were most potent against Aspergillus niger and compound 14 was found to be the most active. Compound 7 showed appreciable anticancer activity against HCT 116, a colon cancer cell line. QSAR analysis indicated the importance of topological parameter, valence third order molecular connectivity index (3χv) and electronic parameter, dipole moment (μ) in describing the antimicrobial activity of the synthesized compounds.

Synthesis, in vitro antimicrobial, anticancer evaluation and QSAR studies of N′-(substituted)-4-(butan-2-lideneamino)benzohydrazides

A series of N′-(substituted)-4-(butan-2-ylideneamino)benzohydrazides (1–21) was synthesized and characterized by physicochemical as well as spectral means. The synthesized compounds were screened for their in vitro antimicrobial and anticancer potentials. The synthesized compounds displayed higher antifungal potential as compared to antibacterial potential. Besides having good antifungal potential, the synthesized compounds were having appreciable anticancer potential and a number of compounds displayed higher anticancer potential than the standard drug, carboplatin. The results of QSAR studies demonstrated the importance of steric parameter, molar refractivity (MR), topological parameters, third order molecular connectivity index (3χ), Kier’s first order shape index (κ1) in describing the antimicrobial activity of N′-(substituted)-4-(butan-2-ylideneamino)benzohydrazides.

4-(1-Aryl-5-chloro-2-oxo-1,2-dihydro-indol-3-ylideneamino)-N-substituted benzene sulfonamides: Synthesis, antimicrobial, anticancer evaluation and QSAR studies

A series of 4-(1-aryl-5-chloro-2-oxo-1,2-dihydro-indol-3-ylideneamino)-N-substituted benzenesulfonamide derivatives (1–20) was synthesized and evaluated for its in vitro antimicrobial and anticancer activities. Antimicrobial results indicated that compounds N-(4-(1-benzoyl-5-chloro-2-oxoindolin-3-ylideneamino) phenylsulfonyl)-4-isopropoxy benzamide (9) and N-(4-(5-chloro-1-(2-chlorobenzoyl)-2-oxoindolin-3-ylideneamino) phenylsulfonyl)-4-isopropoxybenzamide (19) were found to be the most effective ones. The anticancer results indicated that almost all the synthesized compounds were more active than the standard drug carboplatin but less active than the standard drug 5-fluorouracil (5-FU) against both the cell lines (HCT116 and RAW 264.7). 4-(1-Benzoyl-5-chloro-2-oxoindolin-3-ylideneamino)-N-(pyrimidin-2-yl) benzenesulfonamide (3) was found to be most potent and exhibited selectivity toward HCT 116. QSAR studies indicated that antimicrobial activity of isatin derivatives against different microbial strains was governed by lipophilic parameter, log P and topological parameters valance zero and third order molecular connectivity indices (0χv and 3χv).

Synthesis, antimicrobial evaluation and QSAR studies of propionic acid derivatives

A series of Schiff bases (1–17) and esters (18–24) of propionic acid was synthesized in appreciable yield and characterized by physicochemical as well as spectral means. The synthesized compounds were evaluated in vitro for their antimicrobial activity against Gram-positive bacteria Staphylococcus aureus, Bacillus subtilis, Gram negative bacterium Escherichia coli and fungal strains Candida albicans and Aspergillus niger by tube dilution method. Results of antimicrobial screening indicated that besides having good antibacterial activity, the synthesized compounds also displayed appreciable antifungal activity and compound 10 emerged as the most active antifungal agent (pMICca and pMICan=1.93). The results of QSAR studies demonstrated that antibacterial, antifungal and overall antimicrobial activities of synthesized propionic acid derivatives were governed by the topological parameters, Kier’s alpha first order shape index (κα1) and valence first order molecular connectivity index (1χv).

Synthesis, antimicrobial, anticancer, antiviral evaluation and QSAR studies of 4-(1-aryl-2-oxo-1,2-dihydro-indol-3-ylideneamino)-N-substituted benzene sulfonamides

A series of 4-(1-aryl-2-oxo-1,2-dihydro-indol-3-ylideneamino)-N-substituted benzenesulfonamide derivatives (1–32) was synthesized and evaluated for its in vitro antimicrobial, antiviral and cytotoxic activities. Antimicrobial results indicated that compounds (11) and (18) were found to be the most effective ones. In general, the synthesized compounds were bacteriostatic and fungistatic in their action. The cytotoxic screening results indicated that the compounds were less active than the standard drug 5-fluorouracil (5-FU). None of the compounds inhibited viral replication at subtoxic concentrations. In general, the presence of a pyrimidine ring with electron releasing groups and an ortho- and para-substituted benzoyl moiety favored antimicrobial activities. The results of QSAR studies demonstrated the importance of topological parameters, valence zero order molecular connectivity index (0χv) and valence first order molecular connectivity index (1χv) in describing the antimicrobial activity of synthesized compounds.

QSAR studies of antimicrobial activity of 1,3-disubstituted-1H-naphtho[1,2-e][1,3]oxazines using topological descriptors

The antimicrobial activity of 1,3-disubstituted-1H-naphtho[1,2-e][1,3]oxazines was correlated with their physicochemical parameters using Hansch analysis for first time. The QSAR models were developed by both linear and multiple linear regression and the developed models were cross validated by the “leave one out” technique. The QSAR studies indicated that the antibacterial activity of synthesized compounds was governed by topological parameters, Balaban index (J), Kier's second order molecular index (κα2) and third order molecular connectivity index (3χ) and the antifungal activity was governed by valance first order molecular connectivity index (1χv). The practical applicability of developed models was explored by the design of new compounds based on the information derived from the developed equations.

Design, synthesis, antimicrobial, anticancer evaluation, and QSAR studies of 4-(substituted benzylidene-amino)-1,5-dimethyl-2-phenyl-1,2-dihydropyrazol-3-ones

A series of 4-(substituted benzylidene-amino)-1,5-dimethyl-2-phenyl-1,2-dihydropyrazol-3-ones (1–17) was synthesized and tested in vitro for its antimicrobial and anticancer potentials. The biological screening results indicated that compounds having m-chloro substituent on benzaldehyde portion showed antimicrobial potential, whereas compounds having chloro, methoxy, and hydroxyl groups showed anticancer potential. The quantitative structure activity relationship (QSAR) studies indicated the importance of topological parameter, valence first order molecular connectivity index in describing antifungal activity. The developed QSAR models, however, were statistically insignificant with reference to anticancer activity of the synthesized compounds.

Synthesis, antimicrobial evaluation and QSAR studies of 3-ethoxy-4-hydroxybenzylidene/4-nitrobenzylidene hydrazides

Abstract A series of 3-ethoxy-4-hydroxybenzylidene/4-nitrobenzylidene hydrazides ( 1 – 20 ) was synthesized and tested for in vitro antimicrobial activity. The results of antimicrobial studies indicated that the compounds having dinitro, methoxy, hydroxy and nitro substituents on phenyl ring of the aromatic acids were most active ones. The QSAR investigation indicated the importance of the topological parameter, third order molecular connectivity index ( 3 χ ) in describing the antimicrobial activity of synthesized hydrazides.

Topological models for the prediction of antimycobacterial activity of 4-(5-substituted-1,3,4-oxadiazol-2-yl)pyridines

The present study was attempted to predict the antimycobacterial activity of 4-(5-substituted-1,3,4-oxadiazol-2-yl)pyridines. The QSAR studies revealed that topological molecular descriptors best described the antimycobacterial activity of 4-(5-substituted-1,3,4-oxadiazol-2-yl)pyridines. The mt-QSAR models depicted that valence first order molecular connectivity index (1χv) governed the overall antimycobacterial activity of 4-(5-substituted-1,3,4-oxadiazol-2-yl)pyridines. The validation of QSAR models using an external test set revealed that these models can be used for the prediction of antimycobacterial activity of newer 1,3,4-oxadiazole derivatives.