MBZM-N-IBT, a Novel Small Molecule, Restricts Chikungunya Virus Infection by Targeting nsP2 Protease Activity In Vitro, In Vivo, and Ex Vivo.

The increase in disease incidences and persistent Chikungunya virus (CHIKV)-induced arthritis have been a huge burden on public health globally. In the absence of specific antivirals or vaccines, it is essential to continue efforts to develop effective anti-CHIKV strategies. Our previous study showing the in vitro anti-CHIKV potential of a novel molecule 1-[(2-methylbenzimidazol-1-yl) methyl]-2-oxo-indolin-3-ylidene] amino] thiourea (MBZM-N-IBT) encouraged us to further validate its efficacy. Here, the effect of MBZM-N-IBT was evaluated in vitro in RAW 264.7 cells, in vivo in C57BL/6 mice, and ex vivo in human peripheral blood mononuclear cells (hPBMCs). The study demonstrated that CHIKV infection was efficiently abrogated in RAW 264.7 cells (IC50 = 22.34 µM) with significant inhibition in viral proteins. The inhibition was effective in the postentry step, and MBZM-N-IBT predominately interfered in the early stages of CHIKV life cycle. It was further supported when the protease activity of CHIKV-nsP2 was hindered by the compound. Moreover, it diminished the CHIKV-induced inflammatory responses in vitro through significant downregulation of all the major mitogen-activated protein kinases (MAPKs), NF-κB, cyclooxygenase (COX)-2, and cytokines. Furthermore, MBZM-N-IBT restricted CHIKV infection and inflammation in vivo, leading to reduced clinical scores and complete survival of C57BL/6 mice. Additionally, it has been noticed that the CHIKV infection was reduced remarkably in hPBMC-derived monocyte-macrophage populations ex vivo by the compound. In conclusion, it can be suggested that this novel compound MBZM-N-IBT has been demonstrated to be a potential anti-CHIKV molecule in vitro, in vivo, and ex vivo and fulfilled all the criteria to investigate further for successful treatment of CHIKV infection.

Moxifloxacin Derivatives with Potential Antibacterial Activity against Methicillin- Resistant Staphylococcus Aureus (MRSA).

BACKGROUND: Methicillin-resistant S. aureus (MRSA) has already tormented humanity and the environment for a long time and is responsible for many difficult-to-treat infections. Unfortunately, there are limited therapeutic options, and MRSA isolates with complete resistance to vancomycin, the first-line drug for the treatment of MRSA infections, have already emerged in recent years. Moxifloxacin retained activity against mutant bacterial strains with various levels of fluoroquinolones resistance and had a lower potential to select for resistant mutants. Isatin is a versatile structure, and its derivatives are potent inhibitors of many enzymes and receptors. The fluoroquinolone- isatin derivatives demonstrated excellent antibacterial activity against both drug-sensitive and drug-resistant organisms. The structure-activity relationship elucidated that incorporation of 1,2,3-triazole moiety into the C-7 position of fluoroquinolone skeleton was favorable to the antibacterial activity. Accordingly, fluoroquinolone derivatives with isatin and 1,2,3-triazole fragments at the side chain on the C-7 position are promising candidates to fight against drug-resistant bacteria. OBJECTIVE: To explore more active moxifloxacin derivatives to fight against MRSA and enrich the structure-activity relationships. METHODS: The synthesized moxifloxacin derivatives 7a-i and 14a-f were evaluated for their antibacterial activity against a panel of MRSA strains by means of standard two-fold serial dilution method. RESULTS: The majority of the synthesized moxifloxacin derivatives were active against most of the tested MRSA strains with MIC values in a range of 1 to 64 µg/mL. The mechanistic investigations revealed that topoisomerase IV was one of the targets for antibacterial activity. CONCLUSION: These derivatives are useful scaffolds for the development of novel topoisomerase IV inhibitors.

Combined 4D-QSAR and target-based approaches for the determination of bioactive Isatin derivatives.

The hybrid method of the Electron-Conformational Genetic Algorithm (EC-GA) was used to determine the pharmacophore groups and to estimate anticancer activity in isatin derivatives using a robust 4D-QSAR software (EMRE). To build the model, each compound is represented by a set of conformers rather than a single conformation. The Electron Conformational Matrix of Congruity (ECMC) is composed via EMRE software. Electron Conformational Submatrix of Activity (ECSA) was calculated by the comparison of these matrices. Genetic algorithm was used to select important variables to predict theoretical activity. The model with the best seven parameters produced satisfactory results. The E statistics technique was applied to the generated EC-GA model to evaluate the individual contribution of each of the descriptors on biological activity. The r2 and q2 values of the training set compounds were found to be 0.95 and 0.93, respectively. Because no previous 4D-QSAR studies on isatin derivatives have been conducted, this study is important in the development of new isatin derivatives. In this study, 27 isatin derivatives whose activities were estimated using the hybrid EC-GA method were also investigated through molecular docking and molecular dynamics simulations for their BCL-2 inhibitory activity.

Modification with N-benzylisatin restricts stress-induced aggregation of hen egg white lysozyme: Anti-amyloidogenic property of isatin derivative with possible clinical implications.

Hen egg white lysozyme (HEWL) is a structural homolog of human lysozyme and is widely used as a model protein to investigate protein aggregation. The effect of N-benzylisatin on stress-induced aggregation of HEWL has been investigated in the present study. Interaction of the isatin derivative with HEWL induced changes in protein secondary and tertiary structural conformation as evident from different biophysical and spectroscopic studies. In addition, modification with N-benzylisatin was found to increase the conformational stability of HEWL and afford considerable resistance to the protein to stress-induced aggregation as indicated from subsequent experimental studies, including thioflavin T fluorescence, microscopic imaging and dynamic light scattering analysis. Protein modification was analysed and confirmed by MALDI-TOF and ESI-MS studies. The results highlight possible clinical implications of isatin derivative in the treatment of protein misfolding and conformational disorders.

Synthesis, spectroscopic investigation, crystal structure analysis, quantum chemical study, biological activity and molecular docking of three isatin derivatives.

Three isatin derivatives, namely, 1-allyl-3-hydroxy-3-(6-oxocyclohex-1-en-1-yl)indolin-2-one, C17H17NO3, 1-ethyl-3-hydroxy-3-(6-oxocyclohex-1-en-1-yl)indolin-2-one, C16H17NO3, and 5-bromo-3-hydroxy-1-methyl-3-(6-oxocyclohex-1-en-1-yl)indolin-2-one, C15H14BrNO3, were synthesized, crystallized by the slow-evaporation technique, characterized by 1H and 13C NMR spectroscopy, and analysed by the single-crystal X-ray diffraction (XRD) method. Quantum chemical parameters, such as the energy of the highest occupied molecular orbital, energy of the lowest unoccupied molecular orbital, energy gap, electronic energy, ionization potential, chemical potential, global hardness, global softness and electrophilicity index, were calculated. The druglikeness and bioactivity scores of the compounds were calculated. The activities of these isatin derivatives against bacterial strains, such as Eschericia coli, Proteus vulgaris, Shigella flexneri, Staphylococcus aureus and Micrococcus luteus, and the fungal strain Aspergillus niger, were determined using the well-diffusion assay method. Molecular docking studies were carried out to predict the binding mode of the isatin compounds with the penicillin binding protein enzyme and to identify the interactions between the enzyme and the ligands under study.

Inhibition of herpes simplex virus-1 infection by MBZM-N-IBT: in silico and in vitro studies.

INTRODUCTION: The emergence of drug resistance and cross-resistance to existing drugs has warranted the development of new antivirals for Herpes simplex viruses (HSV). Hence, we have designed this study to evaluate the anti-viral activity of 1-[(2-methyl benzimidazole-1-yl) methyl]-2-oxo-indolin-3-ylidene] amino] thiourea (MBZM-N-IBT), against HSV-1. METHOD: Molecular docking was performed to assess the affinity of MBZM-N-IBT for HSV-1 targets. This was validated by plaque assay, estimation of RNA and protein levels as well as time of addition experiments in vitro. RESULT: Molecular docking analysis suggested the inhibitory capacity of MBZM-N-IBT against HSV-1. This was supported by the abrogation of the HSV-1 infectious viral particle formation with the IC50 value of 3.619 µM. Viral mRNA levels were also reduced by 72% and 84% for UL9 and gC respectively. MBZM-N-IBT also reduced the protein synthesis for gC and ICP8 significantly. While mRNA of ICP8 was not significantly affected, its protein synthesis was reduced by 47%. The time of addition experiment revealed the capacity of MBZM-N-IBT to inhibit HSV-1 at early as well as late stages of infection in the Vero cells. Similar effect of MBZM-N-IBT was also noticed in the Raw 264.7 and BHK 21 cells after HSV-1 infection. Supported by the in silico data, this can be attributed to possible interference with multiple HSV targets including the ICP8, ICP27, UL42, UL25, UL15 and gB proteins. CONCLUSION: These results along with the lack of acute oral toxicity and significant anti-inflammatory effects suggest its suitability for further evaluation as a non-nucleoside inhibitor of HSV.

Bis-isatin derivatives: design, synthesis, and biological activity evaluation as potent dimeric DJ-1 inhibitors.

The PARK7 gene (encode DJ-1 protein) was first discovered as an oncogene and later found to be a causative gene for autosomal recessive early onset Parkinson's disease. DJ-1 has been proposed as a potential therapeutic anticancer target due to its pivotal role in tumorigenesis and cancer progression. Based on the homodimer structure of DJ-1, a series of bis-isatin derivatives with different length linkers were designed, synthesized, and evaluated as dimeric inhibitors targeting DJ-1 homodimer. Among them, DM10 with alkylene chain of C10 displayed the most potent inhibitory activity against DJ-1 deglycase. We further demonstrated that DM10 bound covalently to the homodimer of DJ-1. In human cancer cell lines H1299, MDA-MB-231, BEL7402, and 786-O, DM10 (2.5-20 µM) inhibited the cell growth in a concentration-dependent manner showing better anticancer effects compared with the positive control drug STK793590. In nude mice bearing H1299 cell xenograft, intratumor injection of DM10 (15 mg/kg) produced significantly potent tumor growth inhibition when compared with that caused by STK793590 (30 mg/kg). Moreover, we found that DM10 could significantly enhance N-(4-hydroxyphenyl)retinamide-based apoptosis and erastin-based ferroptosis in H1299 cells. In conclusion, DM10 is identified as a potent inhibitor targeting DJ-1 homodimer with the potential as sensitizing agent for other anticancer drugs, which might provide synergistical therapeutic option for cancer treatment.

Co-Inhibition of P-gp and Hsp90 by an Isatin-Derived Compound Contributes to the Increase of the Chemosensitivity of MCF7/ADR-Resistant Cells to Doxorubicin.

Breast cancer is a complex and multi-drug resistant (MDR) disease, which could result in the failure of many chemotherapeutic clinical agents. Discovering effective molecules from natural products or by derivatization from known compounds is the interest of many research studies. The first objective of the present study is to investigate the cytotoxic combinatorial, chemosensitizing, and apoptotic effects of an isatin derived compound (5,5-diphenylimidazolidine-2,4-dione conjugated with 5-substituted isatin, named HAA2021 in the present study) against breast cancer cells (MCF7) and breast cancer cells resistant to doxorubicin (MCF7/ADR) when combined with doxorubicin. The second objective is to investigate the binding mode of HAA2021 withP-glycoprotein (P-gp) and heat shock protein 90 (Hsp90), and to determine whether their co-inhibition by HAA2021 contribute to the increase of the chemosensitization of MCF7/ADR cells to doxorubicin. The combination of HAA2021, at non-toxic doses, with doxorubicin synergistically inhibited the proliferation while inducing significant apoptosis in MCF7 cells. Moreover, HAA2021 increased the chemosensitization of MCF7/ADR cells to doxorubicin, resulting in increased cytotoxicity/selectivity and apoptosis-inducing efficiency compared with the effect of doxorubicin or HAA2021 alone against MCF7/ADR cells. Molecular modeling showed that two molecules of HAA2021 bind to P-gp at the same time, causing P-gp inhibitory effect of the MDR efflux pump, and accumulation of Rhodamine-123 (Rho123) in MCF7/ADR cells. Furthermore, HAA2021 stably interacted with Hsp90α more efficiently compared with 17-N-allylamino-17-demethoxygeldanamycin (17-AAG), which was confirmed with the surface plasmon resonance (SPR) and molecular modeling studies. Additionally, HAA2021 showed multi-target effects via the inhibition of Hsp90 and nuclear factor kappa B (NF-𝜅B) proteins in MCF7 and MCF7/ADR cells. Results of real time-PCR also confirmed the synergistic co-inhibition of P-gp/Hsp90α genes in MCF7/ADR cells. Further pharmacokinetic and in vivo studies are warranted for HAA2021 to confirm its anticancer capabilities.

Recent Advancement of Synthesis of Isatins as a Versatile Pharmacophore: A review.

Isatin (1 H-indole-2, 3-Dione) and its derivatives are versatile compounds which acts as a precursor for a large number of pharmacologically active compounds. Therefore isatins have a significant importance in the synthesis of different heterocyclic compounds. Isatins show variety of biological activities. In this review we focus on synthetic methods of isatins and their biological activities such as antimicrobial, anticonvulsant, anti-inflammatory and analgesic activity, antitubercular activity.

Isatin: A Scaffold with Immense Biodiversity.

Isatin is an endogenous and a significant category of fused heterocyclic components and has widely been a part of several potential biologically useful synthetics. Since its discovery, tons of research work has been conducted with respect to the synthesis, chemical properties, and biological and industrial applications. It contains an indole nucleus having both lactam and keto moiety, which, while being a part of a molecular framework, exerted several biological effects, viz.; anti-microbial, anti-tubercular, anticonvulsant, anti-cancer, etc. Isatin derivatives are synthetically significant substrates, which can be utilized for the synthesis of huge diversified chemical entities of which few members emerged as drugs. The reason for this review is to provide extensive information pertaining to the chemistry and its significance in altering several pathological states of isatin and its derivatives. A Structure-Activity Relationship study thus developed through a gamut of scientific information indicates the importance of mostly electron-withdrawing groups, halogens, nitro, alkoxy, and, to a minor extent, groups with positive inductive effects, such as methyl at position 1, 5, 6 and 7 of isatin in alleviating several clinical conditions. It is also observed from the survey that the presence of two oxo groups at positions 2 and 3 sometimes becomes insignificant as a fusion with a heterocycle at these positions resulted in a biologically relevant compound.

Potent inhibitors of SARS-CoV-2 3C-like protease derived from N-substituted isatin compounds.

SARS-CoV-2 3C-like protease is the main protease of SARS-CoV-2 and has been considered as one of the key targets for drug discovery against COVID-19. We identified several N-substituted isatin compounds as potent SARS-CoV-2 3C-like protease inhibitors. The three most potent compounds inhibit SARS-CoV-2 3C-like protease with IC50's of 45 nM, 47 nM and 53 nM, respectively. Our study indicates that N-substituted isatin compounds have the potential to be developed as broad-spectrum anti-coronavirus drugs.

Indole/isatin-containing hybrids as potential antibacterial agents.

The emergence and worldwide spread of drug-resistant bacteria have already posed a serious threat to human life, creating the urgent need to develop potent and novel antibacterial drug candidates with high efficacy. Indole and isatin (indole-2,3-dione) present a wide structural and mechanistic diversity, so their derivatives possess various pharmacological properties and occupy a salient place in the development of new drugs. Indole/isatin-containing hybrids, which demonstrate a promising activity against a panel of clinically important Gram-positive and Gram-negative bacteria, are privileged scaffolds for the discovery of novel antibacterial candidates. This review, covering articles published between January 2015 and May 2020, focuses on the development and structure-activity relationship (SAR) of indole/isatin-containing hybrids with potential application for fighting bacterial infections, to facilitate further rational design of novel drug candidates.

Hydrophobic substituents on isatin derivatives enhance their inhibition against bacterial peptidoglycan glycosyltransferase activity.

Moenomycin A, the well-known natural product inhibitor of peptidoglycan glycosyltransferase (PGT), is a large amphiphilic molecule of molecular mass of 1583 g/mol and its bioavailablity as a drug is relatively poor. In searching for small-molecule ligands with high inhibition ability targeting the enzyme, we found that the addition of hydrophobic groups to an isatin-based inhibitor of bacterial PGT significantly improves its inhibition against the enzyme, as well as its antibacterial activity. The improvement in enzymatic inhibition can be attributed to a better binding of the small molecule inhibitor to the hydrophobic region of the membrane-bound bacterial cell wall synthesis enzyme and the plasma membrane. In the present study, a total of 20 new amphiphilic compounds were systematically designed and the relationship between molecular hydrophobicity and the antibacterial activity by targeting at PGT was demonstrated. The in vitro lipid II transglycosylation inhibitory effects (IC50) against E. coli PBP1b and MICs of the compounds were investigated. Optimized results including MIC values of 6 µg/mL for MSSA, MRSA, B. subtilis and 12 µg/mL for E. coli were obtained with an isatin derivative 5m which has a molecular mass of 335 g/mol.

Synthesis, anti-proliferative activity, theoretical and 1H NMR experimental studies of Morita-Baylis-Hillman adducts from isatin derivatives.

Quaternary or spirocyclic 3-substituted-3-hydroxy-2-oxindole is considered a privileged scaffold. In other words, it is a molecular core present on several compounds with a wide spectrum of biological activities. Among its precursors, activated ketones (isatin nucleus) can be used as interesting starting points to Morita-Baylis-Hillman adducts derivatives, a class of compounds with good cytotoxic potential. In this paper, we present the synthesis, anti-proliferative activity against lung cancer cell line and a theoretical conformational study of 21 of Morita-Baylis-Hillman adducts from isatin derivatives, by DFT quantum chemical calculations, followed by a SAR and QSAR analysis. Besides, an efficient synthetic protocol and good biological activity profile were highlighted interesting observations about 1H NMR experimental spectra, molecular modeling results and crystallographic data available.

Synthesis, characterization, and antimicrobial activity of some new N-aryl-N'-(2-oxoindolin-3-ylidene)-benzohydrazonamides.

A green approach was developed for synthesizing a series of (isatin-3-ylidene)-hydrazonamides 3a-j from the reaction between isatin, (isatin-3-ylidene)malononitrile, or 2-cyano-2-(2-isatin-3-ylidene)acetate and benzohydrazonamide in ethyl acetate solutions at ambient temperature. The structures of the new compounds were confirmed on the basis of spectral data. In this eco-friendly medium, a variety of (isatin-3-ylidene)hydrazonamides were obtained free of catalyst in good to excellent yields. All the synthesized products were evaluated for their antimicrobial activity. Among the compounds tested, 3b and 3d exhibited good antibacterial activity against Staphylococcus aureus, whereas others responded moderately with reference to the standard drug ciprofloxacin.

Heterogeneous-phase Sonogashira cross-coupling reaction on COC surface for the grafting of biomolecules - Application to isatin.

The grafting of 5-iodoisatin heterocycle on a cyclic olefin copolymer (COC) and a gold surface was performed using a heterogeneous phase Sonogashira reaction consisting of coupling 5-iodoisatin with an arylalkyne previously introduced onto the surfaces. This optimized strategy takes advantage of the well-established methodology to functionalize COC or gold surfaces using aryldiazonium surface chemistry. Herein, we reported the first example of an isatin decorated polymeric or metallic surface. The surfaces were analyzed with a combination of techniques such as IR (Infrared spectroscopy), XPS (X-Ray photoelectron spectroscopy) and SPR (surface plasmon resonance). Docking studies showed that isatin and two derivatives interact with AmiC, a dimeric protein produced by Pseudomonas aeruginosa. Bacterial adhesion on isatin-COC platform was also observed. This general strategy for robust surface functionalization represents an easy approach for patterning surfaces with compounds of biological interest, allowing access to a large panel of original biosensors.

Experimental and Computational Evaluation of Piperonylic Acid Derived Hydrazones Bearing Isatin Moieties as Dual Inhibitors of Cholinesterases and Monoamine Oxidases.

A set of piperonylic acid derived hydrazones with variable isatin moieties was synthesized and evaluated for their inhibitory activity against the enzymes acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and monoamine oxidases A and B (MAO-A/B). The results of in vitro studies revealed IC50 values in the micromolar range, with the majority of the compounds showing selectivity for the MAO-B isoform. N-[2-Oxo-1-(prop-2-ynyl)indolin-3-ylidene]benzo[d][1,3]dioxole-5-carbohydrazide (3) was identified as a lead AChE inhibitor with IC50 =0.052±0.006 µm. N-[(3E)-5-chloro-2-oxo-2,3-dihydro-1H-indol-3-ylidene]-2H-1,3-benzodioxole-5-carbohydrazide (2) was the lead MAO-B inhibitor with IC50 =0.034±0.007 µm, and showed 50 times greater selectivity for MAO-B over MAO-A. The kinetic studies revealed that compounds 2 and 3 displayed competitive and reversible inhibition of AChE and MAO-B, respectively. The molecular docking studies revealed the significance of hydrophobic interactions in the active site pocket of the enzymes under investigation. Further optimization studies might lead to the development of potential neurotherapeutic agents.

A competent synthesis and efficient anti-inflammatory responses of isatinimino acridinedione moiety via suppression of in vivo NF-κB, COX-2 and iNOS signaling.

A potent Nonsterodial Anti-inflammatory Drug (NSAID) candidates has been conceived and built by an assembly of a hydrophilic, fluorescent and COX-2 inhibiting units in the same molecule. The isatinimino-acridinedione core (TM-7) was achieved in a simple three step synthetic procedure viz (i) a multicomponent reaction between dimedone, aldehyde and amine to furnish the nitroacridinedione (4), (ii) reduction step and (iii) schiff's-base condensation with isatin. The excellent anti-inflammatory pharmacological efficiency of the drug was established by in vivo biological experiments. Accordingly, it was found that the treatment with the synthesized isatinimino analogues (dosage: 30 mg/kg) inhibited protein expression of cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and nuclear factor kappa B (NF-κB) as well as production of prostaglandin E2 (PGE2), nitric oxide (NO), tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1ß), and interleukin-6 (IL-6) levels induced by carrageenan. Further, a comparative molecular modeling analysis of TM-7 carried out with the crystal structure of aspirin acetylated human COX-2 suggested effectively binding and efficient accommodation inside the active site's gorge.

Isatin derivatives and their anti-bacterial activities.

Bacterial infections are account for the majority of hospital-acquired and community-acquired infections. The emergency and widespread of drug-resistant pathogens has further worsened the situation. In recent years, various isatin derivatives have been screened for their anti-bacterial activities, and some of them demonstrated promising in vitro and in vivo potency. This review covers the recent advances of isatin derivatives including isatin-azole, isatin-quinoline/quinolone, isatin-furan/coumarin, isatin-hydrazone/(thio)semicarbazone, isatin dimers and isatin-indole hybrids as potential anti-bacterial agents. The enriched structure-activity relationship may pave the way for further rational development of isatin derivatives with broader spectrum, higher potency, lower toxicity and multiple mechanisms of action.

Synthesis of Novel α-amidino Carboxylic Acids and their Use as H-Bond Catalysts in Strecker Reaction.

AIM AND OBJECTIVE: A wide variety of synthesized amidine derivatives are bioactive compounds. They show a vast range of medical properties. Therefore, a simple route for synthesis of novel class of amidine derivatives called amidino carboxylic acids and their use as catalysts in Strecker reaction has been reported in the current work. The stability, local charge density and hydrogen bond parameters were calculated for eight derivatives with different substituents. MATERIALS AND METHODS: In order to synthesize these amidino carboxylic acids, we initially prepared Knovenogel condensation products via the reaction of isatin derivatives with malonitrile. When the reaction was performed in water, the resulting nitrile groups of malonitrile derivatives was hydrolyzed with HOAC/ H2SO4 to generate the desired amide groups. The amide groups in resulting compound converted to amine groups with two Hoffman rearrangements in the presence of NaOH/Br2. Further neutralization led to the final zwitterionic α-amidino carboxylic acids. In the next step, the catalytic activity of these compounds as H-bond donor catalyst was investigated in Strecker reaction. RESULTS: The overall yields of the derivatives with substituent on the aromatic ring of starting isatins are higher than that for the overall yields of nitrogen-substituted isatins. The reaction of 5-nitro isatin with the next reagent gives lower yield in aryl-substituted products. An increase of catalytic activity is observed by rising the electron-withdrawing power of the aromatic ring substituents., The presence of nitro group in the structure of catalyst caused a large increase of catalytic activity in Strecker reaction. DFT calculations at B3LYP/6-31++g(d,p) and Lanl2dz level of theory showed that these compounds act as single H-bond catalysts and higher yields were obtained for complexes with stronger hydrogen bond. CONCLUSION: A simple and efficient method for synthesis of ɑ-amidino carboxylic acids was developed in this research. These compounds have been used as a single H-bond donor catalyst in the Strecker reaction. DFT calculations were carried out to confirm the experimental results. The obtained data from computations are in good agreement with experimental results.