Molecular modelling,synthesis, and antimalarial potentials of curcumin analogues containing heterocyclic ring

The molecular modelling approach was applied to a series of nineteen curcumin analogues to find the possible PfRIO2 kinase inhibitory action. A putative active site in flexible loop (S1) of PfRIO2 kinase was explored computationally to recognize the molecular basis of ligands binding. The ligands (curcumin analogues; 3a–3s) were well accommodated in the selected active site (S1) due to their higher molecular size and length. Further all these synthesized compounds (3a–3s) were evaluated for their in vitro antimalarial activity according to the reported method. The antimalarial data showed that all these compounds to have parasiticidal activity with minimum killing concentrations (MKCs) range between 3.87 and 25.35 μM and schizonticidal activity with IC₅₀ range between 1.48 and 23.09 μM. The compound 3p showed the most significant result with maximum schizonticidal (IC₅₀; 1.48 ± 0.10 μM) and parasiticidal activities (MKC; 3.87 ± 0.36 μM) could be identified as promising lead for further investigations.     

Design,synthesis and biological evaluation of 5-(2-(4-(substituted benzo[d]isoxazol-3-yl)piperazin-1-yl)acetyl)indolin-2-one and 5-(2-(4-substitutedpiperazin-1-yl)acetyl)indolin-2-one analogues as novel anti-tubercular agents

A series of thirty-six novel 5-(2-(4-(benzo[d]isoxazol-3-yl)piperazin-1-yl)acetyl)indolin-2-one and 5-(2-(4-substitutedpiperazin-1-yl)acetyl)indolin-2-one analogues were synthesized, characterized and screened for their in vitro anti-tubercular activity against Mycobacterium tuberculosis H37Rv strain. These compounds exhibited minimum inhibitory concentration between 1.56 and 50 μg/mL. Among these derivatives, compounds 10c, 10d, 10j, 10o and 10v (MIC 6.25 μg/mL) displayed moderate activity, while compounds 10e, 10l, 10q, 10w,10x, 12d, 12e and 12i (MIC 3.12 μg/mL) showed good anti-tubercular activity and compounds 10f, 10k, 10p, 10r, 12f, 12j and 12k (MIC 1.56 μg/mL) exhibited excellent anti-tubercular activity. In addition, MTT assay was accomplished on the active analogues of the series against mouse macrophage (RAW 264.7) cells to evaluate the cytotoxic effect of the newly synthesized compounds and selectivity index of the compounds was determined.     

Synthesis and evaluation of in vitro bioactivity for polysubstituted N-arylpyrazole derivatives

New polysubstituted N-arylpyrazole derivatives were synthesized from N1-arylsydnone with acetylene and boronic acid, including 2-thiophenyl, 3-thiophenyl, 2-benzo[b]thiophenyl, or dibenzothiophenyl-4-boronic acid, via 1,3-dipolar cycloaddition and Suzuki coupling reaction. Based on the growth inhibitory activity results against lung carcinoma (NCI-H226), nasopharyngeal (NPC-TW01), and T-cell leukemia (Jurkat) cancer cells, compounds 5d and 7d with dibenzothiophenyl bioisostere possessed the significant inhibitory activity for NPC-TW01 (32 μM and 16 μM) and NCI-H226 (16 μM and 8.9 μM), respectively.     

Design,synthesis and evaluation of 2-(4-(substituted benzoyl)-1,4-diazepan-1-yl)-N-phenylacetamide derivatives as a new class of falcipain-2 inhibitors

The cysteine protease, falcipain-2 is an important drug target in human malaria parasite Plasmodium falciparum. A new series of 2-(4-(substituted benzoyl)-1,4-diazepan-1-yl)-N-phenylacetamide derivatives 5(a–t) were designed as per pharmacophoric requirements of falcipain-2 inhibitors using ligand-based approach. The target compounds were synthesized from the key intermediate, 2-(1,4-Diazepan-1-yl)-N-phenylacetamide, by coupling it with appropriate carboxylic acids using carbodiimide chemistry. Structural features of target compounds were characterized by spectral data (¹H NMR, and mass) and elemental analyses. The purity of the final compounds was confirmed by HPLC. The compounds were tested for their in vitro falcipain-2 inhibitor activity on recombinant falcipain-2 enzyme. Five compounds 5b, 5g, 5h, 5j, 5k showed good inhibitory activity (>60%), against falcipain-2 at 10 μM concentration, and fifteen compounds showed weak to moderate inhibitor activity. Compound 5g, the most potent compound from this series showed 72% inhibition at 10 μM concentrations.     

Resolution,absolute configuration and antifilarial activity of coumarinyl amino alcohols

The resolution of racemic coumarinyl amino alcohols 5–10 was achieved by using the inexpensive and readily accessible chiral resolving agent N-carbethoxy-l-proline (S)-11. Direct esterification of rac-5–10 with (S)-11 furnished diastereomeric esters, which were easily separated by column chromatography. The obtained diastereomers yielded the desired enantiopure coumarinyl amino alcohols (S)-(+)-5–10 and (R)-(?)-5–10 in good yields with high enantiomeric excess on saponification. The absolute configurations were determined by X-ray crystal analysis and/or by comparison of the specific rotations. Furthermore, in in vitro antifilarial motility inhibition assays, enantiopure coumarins (S)-(+)-9, (R)-(?)-9 and (S)-(+)-10, (R)-(?)-10 were found to be less efficient in affecting the viability of macrofilariae of Brugia malayi than their racemic forms 9 and 10, respectively, indicating the synergistic effect of the enantiomers in evoking antifilarial action.     

Semisynthetic derivatives of haemanthamine and their in vitro antiproliferative activity evaluation against a panel of human cell lines

In this study, a new series of aliphatic, cyclic, and heterocyclic derivatives of haemanthamine was designed and synthesized to enhance its inhibitory effect on the proliferation and viability of cancer cells. A library of haemanthamine derivatives was subjected to 10 μM single-dose cytotoxicity screening against a panel of human cell lines of various histotypes. Initial cytotoxicity evaluation of the parent haemanthamine (1) and a series of twenty-nine (2–30) semisynthetic analogues showed that for some of the newly formed derivatives, a certain cytotoxic effect was observed, in one case even higher than that of the parent compound. Specifically, 11-O-(4-chloro-3-nitrobenzoyl)haemanthamine (21) showed an enhanced antiproliferative effect, where the mean growth percent (GP) value was 5% compared to haemanthamine, leading to a decrease in the GP to 25%. Among ten cell lines tested, derivative 21, bearing a substituted aromatic ester bond via C-11 of haemanthamine, had excellent activity for inhibiting the growth of HeLa (IC₅₀ = 0.2 ± 0.1 μM), A549 (IC₅₀ = 1.7 ± 0.1 μM) and HT-29 (IC₅₀ = 2.2 ± 0.1 μM) cells. When evaluating response kinetics, we found that 21 and haemanthamine dose- and time-dependently suppressed the proliferation of A549 cells. In contrast to haemanthamine (1), Trypan blue and lactate dehydrogenase (LDH) release assay revealed that 21 was capable of reducing the survival of A549 cells.     

Optimization of pyrazolo[1,5-a]pyrimidine based compounds with pyridine scaffold: Synthesis,biological evaluation and molecular modeling study

BackgroundPyrazolopyrimidine heterocycle and its isosteres represent the main scaffold for many pharmacologically active drugs including anti-inflammatory agents. The COX-2 inhibitors are the principal gate for the design of new safe and potent anti-inflammatory agents.MethodsNovel derivatives of pyrazolo[1,5-a] pyrimidines were synthesized and screened in vivo and in vitro for their anti-inflammatory potential.ResultsWithin the constructed compounds, compound 11 was the most active compound on IL-6 and TNF-α (percentage inhibition = 80 and 89%, respectively). In addition, compound 12 displayed the most inhibitory effect towards COX-2 (IC₅₀ = 1.11 µM), whereas compound 11 recorded the highest COX-2 selectivity (S.I = 8.97). The target derivatives 11–14 displayed good edema inhibitory potential (46–68%) and compound 11 was the most potent candidate (ED₅₀ = 35 mg/kg). Additionally, the most potent sPLA2-V inhibitors were compounds 11 and 13 (IC₅₀ = 1 and 1.7 µM respectively). Regarding activity towards 15-LOX, derivative 12 was the most active compound with IC₅₀ = 5.6 µM revealing higher inhibitory activity than nor-dihydroguaiaretic acid (IC₅₀ = 8.5 µM). To confirm the anti-inflammatory potential of the target derivatives, molecular modeling was performed inside COX-2 and 15-LOX active sites.ConclusionDisplay discoveries increment the plausibility that these pyrazolo[1,5-a]pyrimidines might act as a beginning point for the improvement of anti-inflammatory agents.     

Optimized POCl3-assisted synthesis of 2-amino-1,3,4-thiadiazole/1,3,4-oxadiazole derivatives as anti-influenza agents

Although recent decades have witnessed the synthesis of 1,3,4-thiadiazoles via phosphorus POCl₃-promoted cyclization reaction, simultaneous access to 2-amino-1,3,4-thiadiazole and 2-amino-1,3,4-oxadiazole analogs remains unexpected and elusive. Herein, a detailed regiocontrolled synthesis of 2-amino-1,3,4-thiadiazoles in good to high yields with good regioselectivities from readily available thiosemicarbazides using POCl₃ was disclosed. Meantime, to establish a comprehensive structure–activity relationship, 2-amino-1,3,4-oxadiazole derivatives as single regioisomers were prepared via EDCI·HCl-triggered cyclization of the thiosemicarbazide intermediates. The in vitro anti-influenza assays proved that the selected compounds with the pyrazine/pyridine ring exhibited certain inhibitory activities against influenza A virus strains A/HK/68 (H3N2) and A/PR/8/34 (H1N1) in MDCK cells. Among them, N-(adamantan-1-yl)-5-(5-(azepan-1-yl)pyrazin-2-yl)-1,3,4-thiadiazol-2-amine (4j) was the most active compound, and exhibited favorable activity with EC₅₀ values of 3.5 μM and 7.5 μM, respectively. In addition, the molecular docking results explained the reason why compound 4j had dual inhibitory activity and revealed the reasonable binding mode of this compound with the M2-S31N and M2-WT ion channels. This compound had the potential to be further developed as an anti-influenza drug.     

Immobilization of Lecitase® ultra on recyclable polymer support: application in resolution of trans-methyl (4-methoxyphenyl)glycidate in organic solvents

Lecitase® Ultra was immobilized on epoxy-activated polymer (DILBEAD-VWR) functionalized with polyethyleneimine via adsorption and crosslinking with glutaraldehyde. The resolution of methyl trans-(±)-3-(4-methoxyphenyl) glycidate was carried out in xylene (e.e. >99%, conversion 50%). The enzyme is not inhibited by the 4-methoxy phenyl acetaldehyde produced during hydrolysis and the immobilized enzyme with 7% moisture content works efficiently in an organic phase. While the immobilized enzyme can be recycled several times, the polymer support can also be recycled after removing the immobilized enzyme by washing with 1?M HCl.     

Efficient lipase-catalysed route for the kinetic resolution of salsolidine and its ß-carboline analogue

Racemic 1-methyl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline 1 and 1-methyl-1,2,3,4-tetrahydro-ß-carboline 3 were resolved through lipase-catalysed asymmetric acylation on the secondary amino group. High enantioselectivities (E?>200) were observed when the acylation of racemic 1 was performed with phenyl allyl carbonate in the presence of Candida rugosa lipase in toluene at 40?°C or with Candida antarctica lipase B in tert-butyl methyl ether at 50?°C. Excellent enantioselectivity (E?>200) characterised the CAL-B-catalysed acylation of racemic 3 with phenyl allyl carbonate in the presence of triethylamine in tert-butyl methyl ether at 50?°C. The product (R)-carbamates (ee?>97%) were hydrolysed into the corresponding (R)-enantiomers of the free amines 1 and 3 (ee?=?99%) with the use of Pd₂(dba)₃·CHCl₃ catalyst.     

Design,synthesis, crystal structures and biological evaluation of some 1,3-thiazolidin-4-ones as dual CDK2/EGFR potent inhibitors with potential apoptotic antiproliferative effects

A series of novel thiazolidine-4-one derivatives was synthesized by reacting 1,4-disubstituted hydrazine carbothioamides with diethyl azodicarboxylate. The structures were confirmed by spectroscopic data as well as single-crystal X-ray analyses. The antiproliferative activity of the synthesized compounds was investigated against four human cancer cell lines using an MTT assay. Compounds 5d, 5e, and 5f revealed the most potent antiproliferative activity with GI₅₀ values ranging from 0.70 µM to 1.20 µM, compared to doxorubicin GI₅₀ value = 1.10 µM. Compounds 5d, 5e, and 5f were further investigated for their inhibitory activities against CDK2 and EGFR as potential targets for their molecular mechanism. Compounds 5e and 5f have showed potent inhibitory activity to CDK2 enzyme with IC₅₀ values of 18 and 14 nM, which is more potent than the reference dinaciclib (IC₅₀ = 20 nM). Moreover, compounds 5e and 5f were the most potent EGFR inhibitors, with IC₅₀ values of 93 and 87 nM, respectively, compared to the reference erlotinib (IC₅₀ = 70 nM). In addition, the most potent derivatives were tested for their apoptotic activity against caspases 3, 8, and 9, and the results showed that compounds 5d, 5e, and 5f revealed a greater increase in active caspases 3,8 and 9 than doxorubicin. Also, compounds 5d, 5e, and 5f elevated cytochrome C levels in the MCF-7 human breast cancer cell line by about 15.5, 15.8, and 16.5 times, respectively. Finally, a molecular docking study was performed to investigate the binding sites of these compounds within the active sites of CDK2 and EGFR targets, and the results confirmed that the most potent CDK2 and EGFR inhibitor 5h also have showed the highest docking score.     

Bousigonine A and B,bis- and tri-indole alkaloids from Bousigonia mekongensis and their preventing high glucose-induced podocyte injury activity

Bousigonine A (1), an unprecedented eburnamine-voaphylline type dimeric indole alkaloid, and Bousigonine B (2), the first example of eburnamine-eburnamine-aspidospermine type trimeric indole alkaloid were isolated from Bousigonia mekongensis. Their structures were elucidated mainly by spectroscopic analysis and compared to published data. Their preventing high glucose-induced podocyte injury activity were evaluated for the first time, and compound 1 exhibited significant effect with EC₅₀ value of 2.5 μM.     

Syntheses,characterization, in vitro antiglycation and DPPH radical scavenging activities of isatin salicylhydrazidehydrazone and its Mn (II), Co (II), Ni (II), Cu (II), and Zn (II) metal complexes

2-Hydroxy salicylhydrazide isatin hydrazone (L) and its Mn (II), Co (II), Ni (II), Cu (II), and Zn (II), metal complexes were synthesized. ¹H NMR, UV–Vis, IR spectroscopy and elemental (CHN/S) analysis techniques were applied for characterization. TG/DTA techniques revealed that all the synthetic compounds are thermally stable up to 300 °C. They were found non-electrolytes in nature. Furthermore, all these complexes were evaluated for antiglycation and DPPH radical scavenging activities. They showed varying degree of activity with IC₅₀ values between 168.23 and 269.0 μM in antiglycation and 29.63–57.71 μM in DPPH radical scavenging activity. Mn (II), Co (II), Ni (II), Cu (II), and Zn (II), metal complexes showed good antiglycation as well as DPPH radical scavenging activity. The IC₅₀ values for antiglycation activity are 168.23 ± 2.37, 234.27 ± 4.33, 257.1 ± 6.43, 267.7 ± 8.43, 269.0 ± 8.56 Ni for Co, Zn, Mn, Cu, and Ni complexes, respectively, while IC₅₀ value were found to be 29.63 ± 2.76, 31.13 ± 1.41, 35.16 ± 2.45, 43.53 ± 3.12, 57.71 ± 2.61 μM for Cu, Zn, Mn, Co and Ni complexes, respectively, for DPPH radical scavenging activity. These synthesized metal complexes were found to be better active than standards Rutin (IC₅₀ = 294.46 μM) for anti-glycation, and tert-butyl-4-hydroxyanisole (IC₅₀ = 44.7 μM) for DPPH radical scavenging activity.     

Chemical-epigenetic method to enhance the chemodiversity of the marine algicolous fungus, Aspergillus terreus OUCMDZ-2739

Four new meroterpenoids identified as (R)-4-((2,2-dimethylchroman-6-yl)methyl)-3-(4-hydroxyphenyl)-5-methoxyfuran-2(5H)-one (1), 1-(2,2-dimethylchroman-6-yl)-3-(4-hydroxyphenyl)propan-2-one (2), (R,E)-3-(2,2-dimethylchroman-6-yl)-4-hydroxy-5-((2-(2-hydroxypropan-2-yl)-2,3-dihydrobenzofuran-5-yl)methylene)furan-2(5H)-one (3), methyl (R)-2-(2-(2-hydroxypropan-2-yl)-2,3-dihydrobenzofuran-5-yl) acetate (4), along with nine known compounds (5–13) were isolated from a chemical-epigenetic culture of Aspergillus terreus OUCMDZ-2739 with 10 μM trichostatin A (TSA). Under the same condition without TSA, A. terreus OUCMDZ-2739 produced different compounds (14–20), supporting that the chemical-epigenetic modification of fungi could enrich the chemodiversity of the fungal products. The cytotoxicity was observed for compound 8 against K562 cell, 9 against MCF-7 and K562 cells and 12 against MCF-7 cell with IC₅₀ values of 9.5, 10.1, 13.0 and 8.5 μM, respectively. Compounds 3, 8 and 17 exhibited stronger α-glucosidase inhibition than 1-deoxynojirimycin and acarbose (positive controls) with IC₅₀ values of 24.8, 1.2, 61.6, 191.7 and 555.1 μM, respectively. The enzyme kinetics study further indicated that compound 8 was an anticompetitive inhibitor with K_i value of 1.42 μM.     

Design,synthesis and anti-mycobacterial evaluation of some new <Emphasis Type="Italic">N</Emphasis>-phenylpyrazine-2-carboxamides

N-Phenylpyrazine-2-carboxamides (anilides of pyrazinoic acids with simple substituents in various positions) were previously shown to possess significant biological activities in vitro, markedly anti-mycobacterial and photosynthesis-inhibiting activity. Based on structure-activity relationships (SAR) extracted from previously published series, 25 new anilides of non-substituted pyrazinoic acid (POA), 5-CH₃-POA, 6-Cl-POA, 5-tert-butyl-POA and 5-tert-butyl-6-Cl-POA were designed and synthesised. The phenyl part was substituted with simple hydrophobic substituents chosen from methyl and halogens. 5-tert-Butyl-N-(5-fluoro-2-methylphenyl)pyrazine-2-carboxamide (9), N-(3-chloro-4-methylphenyl)-5-methylpyrazine-2-carboxamide (12), 6-chloro-N-(3-chloro-4-methylphenyl)pyrazine-2-carboxamide (13) and 6-chloro-N-(5-iodo-2-methylphenyl)pyrazine-2-carboxamide (18) possessed whole cell anti-mycobacterial activity in vitro against Mycobacterium tuberculosis H37Rv with minimum inhibitory concentration (MIC) of around 10 μM. Importantly, no cytotoxicity in the HepG2 model was detected in vitro at the concentrations tested and the estimated IC50 values were in hundreds of μM, indicating promising selectivity. N-(3-Chloro-4-methylphenyl)pyrazine-2-carboxamide (11) and N-(4-chloro-2-iodophenyl)pyrazine-2-carboxamide (21) exerted significant activity against Mycobacterium kansasii with MIC 12.6 μM and 8.7 μM, respectively. No activity was detected against Mycobacterium avium. SAR were in accordance with those observed for the derivatives previously published.     

Novel 2H-pyrazolo[4,3-c]hexahydropyridine derivatives: Synthesis, crystal structure, fluorescence properties and cytotoxicity evaluation against human breast cancer cells

A series of novel 2H-pyrazolo[4,3-c]hexahydropyridine derivatives (II) have been designed and synthesized. The target compounds have been identified by elemental analysis and spectral (¹H NMR, IR, and MS) data and the absolute configuration of compound (II ₁ ) was confirmed by single crystal X-ray diffraction. The cytotoxicity of the target compounds have been evaluated in vitro against two human breast cancer cell lines MCF-7 and MDA-MB-231 by MTT assay. Most compounds exhibited good inhibition, and compounds II ₂₁ (IC₅₀ = 4.7 μM for MCF-7 and IC₅₀ = 9.3 μM for MDA-MB-231), II ₃₃ (IC₅₀ = 2.4 μM for MCF-7 and IC₅₀ = 4.2 μM for MDA-MB-231) and II ₄₀ (IC₅₀ = 3.3 μM for MCF-7 and IC₅₀ =8.6 μM for MDA-MB-231) displayed better inhibitory activity than 5-fluorouracil (IC₅₀ = 4.8 μM for MCF-7 and IC₅₀ = 9.6 μM for MDA-MB-231, respectively). Flow cytometric analysis and DNA fragmentation suggest that II ₃₃ is cytotoxic and able to induce the apoptosis of MCF-7 cells. The fluorescence properties of compounds II ₁ , II ₆ , II ₁₁ , II ₁₆ , II ₂₃ , II ₂₈ , and II ₃₅ were also studied and compound II ₂₈ afforded the highest photoluminescence quantum yield (38%).     

Exploring facile synthesis and cholinesterase inhibiting potential of heteroaryl substituted imidazole derivatives for the treatment of Alzheimer’s disease

Alzheimer’s disease (AD) is a neurodegenerative disorder and cholinesterase (ChE) enzymes are considered as crucial targets for the treatment of AD. Herein, a series of heteroaryl substituted imidazole derivatives (5a-5x) was prepared using amino acid catalyzed, one-pot facile synthetic approach. In this context, the catalytic potentials of different amino acids were investigated and 15 mol% of glutamic acid was identified as the most suitable catalyst to obtain the target products in good yields up to 90 %. These structurally exciting heterocyclic hybrids were screened against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes. This series displayed moderate to excellent inhibitory potential against AChE with IC₅₀ values > 25 µM and the most active compound was 3-(4-(1-(3,5-dimethylphenyl)-4,5-diphenyl-1H-imidazol-2-yl)-1-phenyl-1H-pyrazol-3-yl)–2H-chromen-2-one (5x) with IC₅₀ value of 25.83 ± 0.25 µM.This inhibitory potential was attributed to hydrophobicity as the major contributory factor. The most potent compound against BChE was 1,3-diphenyl-4-(1,4,5-triphenyl-1H-imidazol-2-yl)-1H-pyrazole (5a) with IC₅₀ value of 0.35 ± 0.02 µM followed by other potent compounds 5p, 5 m, 5x, 5b, 5c, 5e and 5f with IC₅₀ values < 10 µM. SAR studies further revealed that coumarinyl moiety at R¹ position in the imidazolylpyrazole skeleton significantly improved the overall cholinesterase inhibitory potential. However, a simple phenyl ring attached at this R¹ site was highly effective and selective for BChE inhibition (5a) over AChE. Docking data also demonstrated the interaction of 5x and AChE with a docking score of 7564 and atomic contact energy (ACE) value of –291.90 kcal/mol whereas docking score for 5a against BChE was 7096 with ACE value of –332.95 kcal/mol. The results altogether suggest further investigations of the heteroaryl substituted imidazole core skeleton in search of potential leads towards designing of new anti-cholinesterase drugs for the treatment of AD.     

Stereoselective synthesis and anticancer activity of broussonetine analogues

The stereoselective synthesis of two broussonetine analogues 14·HCl and ent-14·HCl with differing stereochemistry of the polyhydroxylated pyrrolidine core and a simple C₁₃ alkyl fragment has been achieved. For their construction, the known oxazolidinones 15 and 16 were chosen as appropriate advanced scaffolds. The common hydrophobic side chain was incorporated at an early stage of the synthesis through Grubbs’ cross metathesis chemistry. The required pyrrolidine skeleton was then formed by the cyclization of open chain intermediates 17 and 18. Four synthesized compounds were screened in vitro for antiproliferative/cytotoxic activity against six cancer cell lines by MTT assay. Compounds 14·HCl (HeLa and A-549) and ent-14·HCl (Caco-2 and Jurkat) showed comparable or higher potency than conventional anticancer agent cisplatin on at least two evaluated cancer cells, respectively.     

Some new protocols for the assignment of absolute configuration by NMR spectroscopy using chiral solvating agents and CDAs

The utility of enantiopure BINOL (1,10-Bi-2-naphthol), in a ternary ion-pair complex, which is obtained using a carboxylic acid and an organic base, as a versatile chiral solvating agent (CSA) has been demonstrated for chiral analysis and the absolute configuration assignment of hydroxy acids. Another protocol where the utility of NOBIN as a CSA has been developed for discrimination and absolute configuration assignment of acids, hydroxy acids and their derivatives with a distinct strategy where a third ingredient, p-toluenesulfonic acid (p-TsOH) serves as a linker. In addition some three component chiral derivatization protocols have been introduced, such as the use of 2-formylphenylboronic acid and enantiopure mandelic acid or a primary amine for the determination of the configuration of primary amines and hydroxy acids, respectively. A simple, rapid and highly efficient three component chiral derivatizing protocol has also been discussed which was developed for assigning the absolute configuration of chiral α-hydroxy acids and their derivatives, which involves the coupling of 2-formylphenylboronic acid with (R)-[1,1-binaphthalene]-2,2-diamine, and (S)-[1,1-binaphthalene]-2,2-diamine separately. In a few examples, the DFT based theoretical calculations have been carried out to determine the geometry optimized structures of the complexes.