Benzimidazol-1-yl-1-phenylpropanone Analogs as Potent Antimicrobial Agents: Rational Design and Synthesis

Designed, synthesized a sequence of novel benzimidazol-1-yl-1-phenylpropanone hybrids and assessed for in vitro antimicrobial potential counter to several bacterial strains. Computational Methodology was carried out for designing of the target molecules and structures were confirmed by spectroscopic analysis. Amid the 12 integrated derivatives, (3-(2-((3-fluorobenzylidene)amino)-1H-benzo[d]imidazol-1-yl)-1-phenylpropan-1-one ( 6g ) and 3-(2-((4-fluorobenzylidene)amino)-1H-benzo[d]imidazol-1-yl)-1-phenylpropan-1-one ( 6k ) were found to acquire excellent antibacterial activity against all bacterial strains (Escherichia coli, Pseudomonas aeruginosa, Bacillus subtilis, Staphylococcus aureus), whereas derivative 3-(2-((2-fluorobenzylidene)amino)-1H-benzo[d]imidazol-1-yl)-1-phenylpropan-1-one ( 6c ), was potent against Escherichia coli, Bacillus subtilis, Staphylococcus aureus and displayed moderate action against P. aeruginosa. Derivatives with NO₂ substituent at 3^rd and 4^th position, 3-(2-((3-nitroobenzylidene)amino)-1H-benzo[d]imidazol-1-yl)-1-phenylpropan-1-one ( 6h ) and 3-(2-((4-nitroobenzylidene)amino)-1H-benzo[d]imidazol-1-yl)-1-phenylpropan-1-one ( 6 l ) respectively declared good to moderate results against all bacterial strains. Further, 3-(2-((3-chlorobenzylidene)amino)-1H-benzo[d]imidazol-1-yl)-1-phenylpropan-1-one ( 6f ) and 3-(2-((4-chlorobenzylidene)amino)-1H-benzo[d]imidazol-1-yl)-1-phenylpropan-1-one ( 6j ) were found to be more competent against both fungal strains (C. albicans, A. niger). Serial two-fold dilution method was used for the entire study and standard drugs utilized were ciprofloxacin and clotrimazole. MIC values (μg/ml) of novel synthesized analogs were reported in comparison to standard drugs for antibacterial and antifungal actions. Molecular docking studies showed that designed molecules dynamically bound with effective area of the receptor (DNA gyrase B, Clotrimazole complex of cytochrome P 45046A1) and in vitro results were in accord with in silico studies.     

Design,Synthesis, Antimicrobial Evaluation and in Silico Studies of Eugenol-Sulfonamide Hybrids

Using molecular hybridization, specific sulfonamide derivatives of eugenol were synthesized with subtle modifications in the allylic chain of the eugenol subunit (and also in the nature of the substituent group in the sulfonamide aromatic ring) which allowed us to study the influence of structural changes on the antimicrobial potential of the hybrids. Antimicrobial test results showed that most of the synthesized hybrid compounds showed good activity with better results than the parent compounds. Molecular docking studies of the hybrids with the essential bacterial enzyme DHPS showed complexes with low binding energies, suggesting that DHPS could be a possible target for the antibacterial sulfonamide-eugenol hybrids. Furthermore, most of the final compounds presented similar docking poses to that of the crystallographic ligand sulfamethoxazole. The results obtained allow us to conclude that these are promising compounds for use as new leads in the search for new antibacterial sulfonamides.     

Synthesis,Anticancer Evaluation and in Silico Studies of 1,4-Dihydropyridines

An efficient 1,4-dihydropyridine synthesis under mild conditions has been developed. Numerous substrates were tested, with yields of 1,4-dihydropridines ranging from good to excellent and a wide range of functional group tolerance. A549, HT-29, and HepG2 cancer cells were used to investigate the anticancer efficacy of each of the produced compounds. Additionally, in-silico docking studies were conducted to understand the structure-based features of the anticancer mechanism with the cancer medication target of Adenosine A2A receptor as well as the molecular level interactions of the compounds.     

Synthesis and Evaluation of Novel Metacetamol Derivatives with Hydrazone Moiety as Anticancer and Antimicrobial Agents

By exploiting the wide biological potential of the hydrazone scaffold, a series of hydrazone derivatives were synthesized, starting from N-(3-hydroxyphenyl)acetamide (metacetamol). The structures of the compounds were determined using IR, ¹H and ¹³C-NMR, and mass spectroscopic methods. The obtained molecules ( 3 a – j ) were evaluated for their anticancer potential against MDA-MB-231 and MCF-7 breast cancer cell lines. According to the CCK-8 assay, all tested compounds showed moderate to potent anticancer activity. Among them, N-(3-(2-(2-(4-nitrobenzylidene)hydrazinyl)-2-oxoethoxy)phenyl)acetamide ( 3 e ) was found to be the most effective derivative with an IC₅₀ value of 9.89 μM against MDA-MB-231 cell lines. This compound was further tested for its potential effects on the apoptotic pathway. Molecular docking studies was also carried out for 3 e in the colchicine binding pocket of tubulin. Additionally, compound 3 e also demonstrated effective antifungal activity, particularly against Candida krusei (MIC=8 μg/ml), indicating that nitro group at the 4^th position of the phenyl ring was the most preferable substituent for both cytotoxic and antimicrobial activity. Our preliminary findings suggest that compound 3 e could be exploited as a leading structure for further anticancer and antifungal drug development.     

Synthesis,Biological Evaluation,and Molecular Modeling Studies of New 1,3,4-Thiadiazole Derivatives as Potent Antimicrobial Agents

In this work, the synthesis, characterization, and biological activities of a new series of 1,3,4-thiadiazole derivatives were investigated. The structures of final compounds were identified using ¹H-NMR, ¹³C-NMR, elemental analysis, and HRMS. All the new synthesized compounds were then screened for their antimicrobial activity against four types of pathogenic bacteria and one fungal strain, by application of the MIC assays, using Ampicilin, Gentamycin, Vancomycin, and Fluconazole as standards. Among the compounds, the MIC values of 4 and 8 μg/mL of the compounds 3f and 3g , respectively, are remarkable and indicate that these compounds are good candidates for antifungal activity. The docking experiments were used to identify the binding forms of produced ligands with sterol 14-demethylase to acquire insight into relevant proteins. The MD performed about 100 ns simulations to validate selected compounds’ theoretical studies. Finally, using density functional theory (DFT) to predict reactivity, the chemical characteristics and quantum factors of synthesized compounds were computed. These results were then correlated with the experimental data. Furthermore, computational estimation was performed to predict the ADME properties of the most active compound 3f .     

Targeting Colon Cancer Cells with Pyrazino-Imidazolinone Derivatives: Synthesis,Molecular Docking,and in Vitro Evaluation of Anti-Proliferative and Pro-Apoptotic Activities

We report the synthesis, spectroscopic characterization, molecular docking and biological evaluation of nine pyrazino-imidazolinone derivatives. These derivatives were evaluated for their anticancer activity against three cancer cell lines: 518A2 melanoma, HCT-116, and HCT-116 p53 knockout mutant colon carcinoma. The MTT assay was employed to assess their effectiveness. Among the nine compounds tested, four compounds (5 a, 5 d, 5 g, and 5 h) exhibited promising antiproliferative activity specifically against HCT-116 p53-negative cells (IC₅₀ 0.23, 0.20, 2.07 and 58.75 μM, respectively). Interestingly, treatment with the 3,4-dimethoxyphenyl derivative 5a resulted in a significant increase (199 %) in caspase activity in HCT-116 p53-negative cells compared to untreated cells while the bromo-pyrazine derivative 5d demonstrated (190 %) increase. These findings suggest that compounds 5a and 5 d induce p53-independent apoptotic cell death. Additionally, in silico molecular docking studies with EGFR and tyrosinase proteins indicated that compounds 5 d and 5 e have the potential to bind to important anticancer drug targets.     

Design,Synthesis and Cytotoxicity of New Coumarin-1,2,3-triazole Derivatives: Evaluation of Anticancer Activity and Molecular Docking Studies

A library of new coumarin-1,2,3-triazole hybrids 7a – l were synthesized from 4-(diethylamino)-2-hydroxybenzaldehyde precursor through a series of reactions including Vilsmeier-Haack reaction and condensation reaction to achieve key intermediate oxime and further performed click reaction by using different aromatic azides. We screened all molecules in silico against crystal structure of Serine/threonine-protein kinase 24 (MST3), based on these results all molecules were screened for their cytotoxicity against human breast cancer MCF-7 and lung cancer A-549 cell lines. Compound 7 b (p-bromo) showed best activity against both cell lines MCF-7 and A-549 with IC₅₀ value of 29.32 and 21.03 μM, respectively, in comparison to Doxorubicin corresponding IC₅₀ value of 28.76 and 20.82 μM. Another compound 7 f (o-methoxy) also indicated good activity against both cell lines with IC₅₀ value of 29.26 and 22.41 μM. The toxicity of all compounds tested against normal HEK-293 cell lines have not shown any adverse effects.     

Chemical Characterization,Antioxidant, Antimicrobial,Cytotoxicity and in Silico Studies of Hexane Extract and Essential Oils from Citrus limon Leaves

The present study investigates the chemical composition, antioxidant and antimicrobial bioactivities of essential oil and hexane extract from Citrus limon leaves. The isolation of essential oil was carried out using the Clevenger apparatus. The percentage yield of essential oil and hexane extract from Citrus limon leaves was 0.59 and 0.50 %, respectively. 2,2-Diphenyl-1-picrylhydrazyl (DPPH) scavenging assay highlighted that Citrus limon leaves essential oil (CLEO) and hexane extract exhibited the significant antioxidant potential of 69.64 and 67.55 %, respectively, compared to the BHT standard. Similarly, a significant inhibition in linoleic acid peroxidation was recorded in both CLEO (81.93 %) and hexane extract (50.34 %). Characterization of chemical constituents in CLEO and extract was executed using GC/MS, where Limonene was detected as a major compound in CLEO (60.52 %) and hexane extract (73.62 %). The haemolytic activity ranged from 2.46 to 5.75 % revealing negligible cytotoxicity of CLEO and hexane extract. In silico studies agree with the in vitro antimicrobial studies, where vinimalol, taraxasterol, and moretenol present in CLEO showed strong interactions/inhibition against dihydroorotase and DNA gyrase from E. coli, and the tyrosyl-tRNA synthetase and DNA gyrase from S. aureus. Based on the current data, it may be concluded that both CLEO and hexane extract possessed significant bioactivities, such as antimicrobial and antioxidant activity, with minimal cytotoxicity.     

Design,in Silico Studies and Biological Evaluation of New Chiral Thiourea and 1,3-Thiazolidine-4,5-dione Derivatives

In this study, new chiral thiourea and 1,3-thiazolidine-4,5-dione derivatives were synthesized, it was aimed to evaluate the various biological activities and molecular docking of these compounds. Firstly, the new thioureas ( 1 – 16 ) were obtained by reacting 1-naphthylisothiocyanate with different chiral amines. Then, the chiral thioureas were cyclized with oxalyl chloride to obtain 1,3-thiazolidine-4,5-dione derivatives ( 17 – 32 ). All compounds were evaluated with several in vitro antioxidant and enzyme inhibition activities. Compound 30 was the most active compound against AChE, with a value of IC₅₀=8.09±0.58 μM. On the other hand, all compounds were tested in silico absorption, distribution, metabolism, and excretion (ADME) assays to better understand their bioavailability. These physicochemical properties, pharmacokinetics, and drug-likeness of all compounds were calculated using SwissADME. Furthermore, according to molecular docking analyses compound 30 exhibited significant binding affinities for all enzymes. Based on our overall observations, compound 30 could be recommended as a potential lead for the therapuetic of Alzheimer's.     

Synthesis of Imidazole-2,3-dihydrothiazole Compounds as VEGFR-2 Inhibitors and Their Support with in Silico Studies

In this study, 12 novel 2-((1-(4-(1H-imidazol-1-yl)phenyl)ethylidene)hydrazineylidene)-3-ethyl-4-(substitutephenyl)-2,3-dihydrothiazole derivatives were obtained. Among these compounds, 2-((1-(4-(1H-imidazol-1-yl)phenyl)ethylidene)hydrazineylidene)-4-([1,1′-biphenyl]-4-yl)-3-ethyl-2,3-dihydrothiazole ( 4h ) was chosen as the most active derivative in the series. According to the MTT results, compounds 4h and 4k showed activity with IC₅₀=4.566±0.246 μM and IC₅₀=4.537±0.463 μM, respectively. Unlike other derivatives, compound 4h carries a phenyl ring in the 4th position of the phenyl ring. This bulky group allowed the compound to settle in the enzyme active site. Dynamic studies show that the stability of the compound does not change over 40 ns. RMSD, RMSF and Rg parameters all remained within acceptable limits. The uninterrupted aromatic hydrogen bonding of the enzyme active site with the important amino acids Cys919, Glu885 and Asp1046 proves the inhibitory potential of compound 4h on the VEGFR-2 enzyme. It is thought that more active compounds will be reached with the derivatives to be synthesized starting from compound 4h .     

Design,Synthesis, and Biological Evaluation of Novel Indanone Derivatives as Cholinesterase Inhibitors for Potential Use in Alzheimer's Disease

Indanone derivatives containing meta/para-substituted aminopropoxy benzyl/benzylidene moieties were designed based on the structures of donepezil and ebselen analogs as the cholinesterase inhibitors. The designed compounds were synthesized and their acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities were measured. Inhibitory potencies (IC₅₀ values) for the synthesized compounds ranged from 0.12 to 11.92 μM and 0.04 to 24.36 μM against AChE and BChE, respectively. Compound 5 c showed the highest AChE inhibitory potency with IC₅₀ value of 0.12 μM, whereas the highest BChE inhibition was achieved by structure 7 b (IC₅₀=0.04 μM). Structure-activity relationship (SAR) analysis revealed that there is no significant difference between meta and para-substituted derivatives in AChE and BChE inhibition. However, the most potent AChE inhibitor 5 c belongs to meta-substituted compounds, while the most active BChE inhibitor is para-substituted derivative 7 b . The order of enzyme inhibition potency based on the substituted amine group is dimethyl amine>piperidine>morpholine. Compounds containing C=C linkage are more potent AChE inhibitors than the corresponding saturated structures. Molecular docking studies indicated that 5 c interacts with AChE in a very similar way to that observed experimentally for donepezil. The introduced indanone-aminopropoxy benzylidenes could be used in drug-discovery against Alzheimer's disease.     

Synthesis of the N‐methyl Derivatives of 2‐Aminothiazol‐4(5H)‐one and Their Interactions with 11βHSD1‐Molecular Modeling and in Vitro Studies

11β‐Hydroxysteroid dehydrogenase type 1 (11β‐HSD1) is an enzyme that affects the body's cortisol levels. The inhibition of its activity can be used in the treatment of Cushing's syndrome, metabolic syndrome and type 2 diabetes. In this study, we synthesized new derivatives of 2‐(methylamino)thiazol‐4(5H)‐one and tested their activity towards inhibition of 11β‐HSD1 and its isoform – 11β‐HSD2. The results were compared with the previously tested allyl derivatives. We found out that methyl derivatives are weaker inhibitors of 11β‐HSD1 in comparison to their allyl analogs. Due to significant differences in the activity of the compounds, molecular modeling was performed, which was aimed at comparing the interactions between 11β‐HSD1 and ligands differing by substituent at the amine group (allyl vs. methyl). Modeling showed that the absence of the allyl group can lead to the rotation of whole ligand molecule which affects its interaction with the enzyme.     

Salophen Copper(II) Complex‐Assisted Click Reactions for Fast Synthesis of 1,2,3‐Triazoles Based on Naphthalene‐1,4‐dione Scaffold,Antibacterial Evaluation,and Molecular Docking Studies

The salophen copper(II) complex was successfully used for the efficient synthesis of new 1,2,3‐triazoles based on the naphthalene‐1,4‐dione scaffold. The reaction of 2‐chloro‐3‐(prop‐2‐yn‐1‐yloxy)naphthalene‐1,4‐dione or 2,3‐bis(prop‐2‐yn‐1‐yloxy)naphthalene‐1,4‐dione with aromatic azides in the presence of a low copper catalyst (loading 1 mol‐%) afforded 2‐chloro‐3‐[(1‐phenyl‐1H‐1,2,3‐triazol‐4‐yl)methoxy]naphthalene‐1,4‐dione or 2,3‐bis[(1‐phenyl‐1H‐1,2,3‐triazol‐4‐yl)methoxy]naphthalene‐1,4‐dione, respectively. The advantages of these reactions are short reaction times, high‐to‐excellent reaction yields, operational simplicity, and mild experimental conditions. The new 1,2,3‐triazoles obtained were screened for their in vitro antibacterial activities and were subjected to molecular docking studies.     

New 2‐Oxoimidazolidine Derivatives: Design,Synthesis and Evaluation of Anti‐BK Virus Activities in Vitro

A series of novel 2‐oxoimidazolidine derivatives were synthesized and their antiviral activities against BK human polyomavirus type 1 (BKPyV) were evaluated in vitro. Bioassays showed that the synthesized compounds 1‐{[(4E)‐5‐(dichloromethylidene)‐2‐oxoimidazolidin‐4‐ylidene]sulfamoyl}piperidine‐4‐carboxylic acid ( 5 ) and N‐Cyclobutyl‐N′‐[(4E)‐5‐(dichloromethylidene)‐2‐oxoimidazolidin‐4‐ylidene]sulfuric diamide ( 4 ) exhibited moderate activities against BKPyV (EC₅₀=5.4 and 5.5 μm , respectively) that are comparable to the standard drug Cidofovir. Compound 5 exhibited the same cytotoxicity in HFF cells and selectivity index (SI₅₀) as Cidofovir. The selectivity index of compound 4 is three times less than that of Cidofovir due to the higher toxicity of this compound. Hence, these compounds may be taken as lead compound for further development of novel ant‐BKPyV agents.     

Synthesis and Characterization of Novel 1,3-Diaryltriazene-Substituted Sulfaguanidine Derivatives as Selective Carbonic Anhydrase Inhibitors: Biological Evaluation,in Silico ADME/T and Molecular Docking Study

Sulfonamide compounds known as human carbonic anhydrase (hCA) inhibitors are used in the treatment of many diseases such as epilepsy, antibacterial, glaucoma, various diseases. 1,3-diaryl-substituted triazenes and sulfaguanidine are used for therapeutic purposes in many drug structures. Based on these two groups, the synthesis of new compounds is important. In the present study, the novel 1,3-diaryltriazene-substituted sulfaguanidine derivatives ( SG1-13 ) were synthesized and fully characterized by spectroscopic and analytic methods. Inhibitory effect of these compounds on the hCA I and hCA II was screened as in vitro. All the series of synthesized compounds have been identified as potential hCA isoenzymes inhibitory with K_I values in the range of 6.44±0.74-86.85±7.01 nM for hCA I and with K_I values in the range of 8.16±0.40-77.29±9.56 nM for hCA II. Moreover, the new series of compounds showed a more effective inhibition effect than the acetazolamide used as a reference. The possible binding positions of the compounds with a binding affinity to the hCA I and hCA II was demonstrated by in silico studies. In conclusion, compounds with varying degrees of affinity for hCA isoenzymes have been designed and as selective hCA inhibitors. These compounds may be potential alternative agents that can be used to treat or prevent diseases associated with glaucoma and hCA inhibition.     

Synthesis,Crystal Structure,and in Vitro Biological Evaluation of C-6 Pyrimidine Derivatives: New Lead Structures for Monitoring Gene Expression in Vivo

Novel C-6 substituted pyrimidine derivatives are good substrates of herpes simplex virus type 1 thymidine kinase (HSV1-TK). Enzyme kinetic experiments showed that our lead compound, N-methyl DHBT (N-methyl-6-(1,3-dihydroxyisobutyl) thymine; N-Me DHBT), is phosphorylated at a similar rate compared to “gold standard” 9-[4-fluoro-3-(hydroxymethyl)butyl]guanine, FHBG, (K _m = 10 ± 0.3 μM; k _cat = 0.036 ± 0.015 sec^?1). Additionally, it does not show cytotoxic properties on B16F1 cells up to a concentration of 10 mM. The x-ray analysis of the crystal structures of HSV1-TK with N-Me DHBT and of HSV1-TK with the fluorinated derivative N-Me FHBT confirmed the binding mode predicted by docking studies and their substrate characteristics. Moreover, the crystal structure of HSV1-TK with N-Me DHBT revealed an additional water-mediated H-bond interesting for the design of further analogues.     

1,2,3‐Triazole Tagged 3H‐Pyrano[2,3‐d]pyrimidine‐6‐carboxylate Derivatives: Synthesis,in Vitro Cytotoxicity,Molecular Docking and DNA Interaction Studies

A series of novel ethyl 2,7‐dimethyl‐4‐oxo‐3‐[(1‐phenyl‐1H‐1,2,3‐triazol‐4‐yl)methyl]‐4,5‐dihydro‐3H‐pyrano[2,3‐d]pyrimidine‐6‐carboxylate derivatives 7a – 7m were efficiently synthesized employing click chemistry approach and evaluated for in vitro cytotoxic activity against four tumor cell lines: A549 (human lung adenocarcinoma cell line), HepG2 (human hematoma), MCF‐7 (human breast adenocarcinoma), and SKOV3 (human ovarian carcinoma cell line). Among the compounds tested, the compounds 7a , 7b , 7f , 7l , and 7m have shown potential and selective activity against human lung adenocarcinoma cell line (A549) with IC₅₀ ranging from 0.69 to 6.74 μm . Molecular docking studies revealed that the compounds 7a , 7b , 7f , 7l , and 7m are potent inhibitors of human DNA topoisomerase‐II and also showed compliance with stranded parameters of drug likeness. The calculated binding constants, k_b, from UV/VIS absorptional binding studies of 7a and 7l with CT‐DNA were 10.77 × 10⁴, 6.48 × 10⁴, respectively. Viscosity measurements revealed that the binding could be surface binding mainly due to groove binding. DNA cleavage study showed that 7a and 7l have the potential to cleave pBR322 plasmid DNA without any external agents.     

Quinazolin‐4(3H)‐one‐Based Hydroxamic Acids: Design,Synthesis and Evaluation of Histone Deacetylase Inhibitory Effects and Cytotoxicity

The present article describes the synthesis and biological activity of various series of novel hydroxamic acids incorporating quinazolin‐4(3H)‐ones as novel small molecules targeting histone deacetylases. Biological evaluation showed that these hydroxamic acids were potently cytotoxic against three human cancer cell lines (SW620, colon; PC‐3, prostate; NCI?H23, lung). Most compounds displayed superior cytotoxicity than SAHA (suberoylanilide hydroxamic acid, Vorinostat) in term of cytotoxicity. Especially, N‐hydroxy‐7‐(7‐methyl‐4‐oxoquinazolin‐3(4H)‐yl)heptanamide ( 5b ) and N‐hydroxy‐7‐(6‐methyl‐4‐oxoquinazolin‐3(4H)‐yl)heptanamide ( 5c ) (IC₅₀ values, 0.10–0.16 μm ) were found to be approximately 30‐fold more cytotoxic than SAHA (IC₅₀ values of 3.29–3.67 μm ). N‐Hydroxy‐7‐(4‐oxoquinazolin‐3(4H)‐yl)heptanamide ( 5a ; IC₅₀ values of 0.21–0.38 μm ) was approximately 10‐ to 15‐fold more potent than SAHA in cytotoxicity assay. These compounds also showed comparable HDAC inhibition potency with IC₅₀ values in sub‐micromolar ranges. Molecular docking experiments indicated that most compounds, as represented by 5b and 5c , strictly bound to HDAC2 at the active binding site with binding affinities much higher than that of SAHA.     

Molecular Docking and Interaction Studies of Identified Abscisic Acid Receptors in Oryza sativa: An In-Silico Perspective on Comprehending Stress Tolerance Mechanisms

BackgroundAbiotic stresses affect plants in several ways and as such, phytohormones such as abscisic acid (ABA) play an important role in conferring tolerance towards these stresses. Hence, to comprehend the role of ABA and its interaction with receptors of the plants, a thorough investigation is essential.AimThe current study aimed to identify the ABA receptors in Oryza sativa, to find the receptor that binds best with ABA and to examine the mutations present to help predict better binding of the receptors with ABA.MethodsProtein sequences of twelve PYL (Pyrabactin resistance 1) and seven PP2C (type 2C protein phosphatase) receptors were retrieved from the Rice Annotation Project database and their 3D structures were predicted using RaptorX. Protein-ligand molecular docking studies between PYL and ABA were performed using AutoDock 1.5.6, followed by 100ns molecular dynamic simulation studies using Desmond to determine the acceptable conformational changes after docking via root mean square deviation RMSD plot analysis. Protein-protein docking was then carried out in three sets: PYL-PP2Cs, PYL-ABA-PP2C and PYL(mut)-ABA-PP2C to scrutinize changes in structural conformations and binding energies between complexes. The amino acids of interest were mapped at their respective genomic coordinates using SNP-seek database to ascertain if there were any naturally occurring single nucleotide polymorphisms (SNPs) responsible for triggering rice PYLs mutations.ResultsInitial protein-ligand docking studies revealed good binding between the complexes, wherein PYL6-ABA complex showed the best energy of -8.15 kcal/mol. The 100ns simulation studies revealed changes in the RMSD values after docking, indicating acceptable conformational changes. Furthermore, mutagenesis study performed at specific PYL-ABA interacting residues followed by downstream PYL(mut)-ABA-PP2C protein-protein docking results after induction of mutations demonstrated binding energy of -8.17 kcal/mol for PP2C79-PYL11-ABA complex. No naturally occurring SNPs that were responsible for triggering rice PYL mutations were identified when specific amino acid coordinates were mapped at respective genomic coordinates.ConclusionThus, the present study provides valuable insights on the interactions of ABA receptors in rice and induced mutations in PYL11 that can enhance the downstream interaction with PP2C.