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A proficient copper(i) catalyzed one pot synthetic protocol has been established to synthesize medicinally essential substituted imidazo[1,2-a]pyridines via C–H bond amination followed by acetylene incorporation under microwave irradiation.

A series of 2-aryl-5-[4-(1H-pyrrol-1-yl)phenyl]-1,3,4-oxadiazole derivatives (VIa-g) have been synthesized in good yields. These compounds were synthesized with an approach to reduce the growing anti-tubercular resistance and to develop more potent and less side effects having antitubercular activity. The reaction of 2,5-dimethoxytetrahydro furan with 4-aminobenzoate (II) in presence of ethanol, which yields ethyl 4-pyrrol-1-yl benzoate (III). This ethyl-4-pyrrol-1-yl benzoate (III) on reaction with hydrazine hydrate produced 4-pyrrol-1-yl benzoic acid hydrazide (IV). This carbohydrazide on treatment with different substituted benzoyl chlorides gave intermediates (Va-g), which on cyclisation with P2O5 in the presence of DMF yielded of 2-aryl-5-[4-(1Hpyrrol-1-yl)phenyl]-1,3,4-oxadiazoles VI(a-g). Structure of newly synthesized pyrrole derivatives were confirmed on the basis of physicochemical and spectral data (IR, 1H-NMR, 13C-NMR and Mass spectra). All the synthesized compounds were screened for their antitubercular activity using Microplate Alamar Blue Assay (MABA) method. Compounds showed anti-tubercular activity at MIC values between 1.6 to 12.5 µg/ml, compounds VIb,VIc and VId showed highest activity of 1.6 µg/ml. Selected compounds were evaluated for anti-bacterial activity against gram positive (S. aureus) and gram negative (E. coli). Compounds showed moderate activity. Physicochemical properties of the selected compounds satisfieds with the Lipinski’s rule of 5.

New series of pyrrolylpyranopyrazole were synthesized by reacting with (one pot synthesis) ethyl acetoacetate in aqueous ethanol (1), hydrazine hydrate (2), substituted aldehydes (3a-g), malononitrile (4) and triethylamine’s base stirring for 5hr the solid precipitate was obtained, it has been filtered and washed with cold water to give 6-amino-3-methyl-4-substituted phenyl-1,3a,4,7a-tetrahydropyrano [2,3-c] pyrazole-5-carbonitrile (5a-g). Further it is reacted with 4- pyrrol-1-yl benzoic acid (6) with substituted pyranopyrazoline presence of HBTU and DIEA which resulting in formation of substituted N-5-cyano-3-methyl-4-substituted phenyl 1,3a,47a-tetrahydropyrano [2,3-c] pyrazol-6-yl)-4-(1H-pyrrol-1-yl) benzamides (7a-g) was obtained. All newly synthesized compounds were confirmed by TLC and melting point. The structure of the all newly synthesized compounds were confirmed by spectral study such as IR, 1H NMR, 13C NMR and Mass spectroscopy. The newly synthesized compounds were screened for their antibacterial and antitubercular activities. Compounds exhibited antitubercular activity in the range of 1.6 to 25 µg/ml (MIC). Compounds showed antibacterial activity in the range of 0.8 to 100 µg/ml (MIC). It was indeed very much encouraging to note that most of the compounds have shown better and significant antibacterial and antitubercular activities.

The various novel nitrogen containing heterocyclic compounds were synthesized and are screened for antibacterial and antitubercular activities, purity of newly synthesized compounds confirmed by using TLC and structures for the same compounds were confirmed by using IR, NMR, 13C and Mass spectrum. Pyrrole ring was constructed by reacting benzocaine with 2, 5-dimethoxytetrahydrofuran in presence of glacial acetic acid to obtain ethyl 4-pyrrol-1-ylbenzoate (2) in good yield. Conversion of ethyl 4-pyrrol-1-ylbenzoate (2) into 4-pyrrol-1-yl-benzoic acid hydrazide (3), which was achieved by refluxing ethyl 4-pyrrol-1-ylbenzoate (2) with hydrazine hydrate in ethanol. Then this 4-pyrrol-1-yl-benzoic acid hydrazide (3) treated with appropriate benzaldehyde in presence of TCCA and ethanol to yield compound substituted 2-(4-(1H-pyrrol-1-yl)phenyl)-5-phenyl-1,3,4-oxadiazole 04(a-f).Structures of newly synthesized compounds were confirmed on the basis of physico-chemical and spectral data (IR, 1H &13C-NMR, Mass spectra). All the synthesized compounds were screened for anti-tubercular activity using Microplate Almar Blue Assay (MABA) method. Compounds showed anti-tubercular activity at MIC values between 50 to 3.12 µg/ml when compared with standard drugs Pyrazinamide (3.125 µg/ml) and Streptomycin (6.25 µg/ml).Newly synthesised compounds were also screened for antibacterial activity using broth micro dilution assay method. Compounds showed antibacterial activity at MIC values between 25 to 0.8 µg/ml when compared with standard drugs Ciprofloxacin and Norfloxacin.

4-((4-((Benzo[d]oxazol-2-ylthio)methyl)-1H-1,2,3-triazol-1-yl)methyl)-2H-chromen-2-ones 7k–z were synthesized by conventional as well as microwave irradiation method in order to obtain antimicrobia...

In this paper, the synthesis of novel pyrazoles and their in vitro anti-inflammatory and in-vitro antifungal assay have been reported. These compounds were docked into the inducible nitric oxide sy...

Thiazolidinedione (TZD) based medications have demonstrated to enhance the insulin sensitivity control, hyperglycemia, and lipid metabolism in patients with type 2 diabetes. Hence, in this study, a new series of novel coumarin-4-yl-1,2,3-triazol-4-yl-methyl-thiazolidine-2,4-diones (TZD1-TZD18) were synthesized via copper (I)-catalyzed azide-alkyne cycloaddition "Click Chemistry". The synthesized compounds were evaluated for their glucose uptake assay and in vitro cytotoxicity against HEK-293 (human embryonic kidney) cells which were compared with the standard drug Pioglitazone. Further, molecular docking analysis of these compounds was carried out to explain the in vitro results with PPARγ (PDB ID: 3CS8) and to better understand the bonding interactions with the target protein. The outcomes of in vitro assessment, molecular docking, and pharmacokinetics of the title compounds were revealed to be highly correlated. Interestingly, the compounds TZD4, TZD10, TZD14 and TZD16 were most efficient in lowering the blood glucose level compared with standard drug.

Enoyl Acyl Carrier Protein (ACP) Reductase, a key enzyme, which catalyzes the last reductive step of fatty acid biosynthesis and it, is one of the key enzymes for the development of antitubercular agents. In this pursuit, molecular docking and 3D-QSAR studies (CoMFA and CoMSIA) have been performed on a series of pyrimidine derivatives (29 compounds) to understand the binding sites, interactions to improve over the existing leads in terms of improved biological and physico-chemical properties. Molecular docking was performed on a protein InhA (T2A mutant) (PDB ID: 5OIR) using the Surflex-Dock suite available in SYBYL-X 2.1.1 (Tripose Inc., USA). In addition, 3D-QSAR studies have been performed to validate the models using the data set, which was segregated into training and test set by using the Diversity and Dissimilarity method. Structural features required for the prediction of better inhibitory potency was generated in the form of contour maps from the CoMFA and CoMSIA models (Steric, Electrostatic, Hydrophobicity, H-bond donor and acceptor maps) and predicted values for r2 = 0.966, q2 = 0.22 for the CoMFA model and r2 = 0.925, q2 = 0.576 for the CoMSIA model. From this study, it is observed that interaction with amino acid residues TYR158, MET199, MET161, GLY96, and PHE97 are important for the activity that helped to predict SARs by providing important structural features. Both the models were good in understanding the specific activity of some of the compounds that will facilitate to develop new types of Enoyl ACP reductase inhibitors.

For this work, two series of new piperazine derivatives (3a-o) and triazolo-pyrazine derivatives (3p-t) were synthesized in a single-step reaction. All twenty adducts were obtained in good to high yields and fully characterized by 1H NMR, 13C NMR, IR, and mass spectrometry techniques. To further confirm the chemical identity of the adducts, a crystal of N-{[(4-chlorophenyl)-3-(trifluoromethyl)]-5,6-dihydro-[1,2,4]triazolo[4,3-a]}pyrazine-7(8H)-carboxamide (3t) was prepared and analyzed using X-ray crystallography. In vitro screening of the antimicrobial activity of all compounds (3a-t) was evaluated against five bacterial and two fungal strains. This study disclosed that N-{[(3-chlorophenyl)]-4-(dibenzo[b,f][1,4]thiazepin-11-yl)}piperazine-1-carboxamide (3o) was the superior antimicrobial with good growth inhibition against A. baumannii. Furthermore, the results from the performed molecular docking studies were promising, since the observed data could be used to develop more potent antimicrobials.

Objective In the present study a series of eleven bis-heterocyclic compounds with indole derivative carrying 1,2,4-triazole moiety were synthesized and assessed for their in vitro α-amylase and α-glucosidase inhibition activity. Method The synthesized compounds were characterized by using various spectroscopic techniques such as 1H NMR, IR and EI-MS. Initial in silico screening process was used to find potential ligands that were later evaluated for α-amylase and α-glucosidase inhibitory potential. Results The docking results revealed that the synthesized compounds were well accommodated in the binding pockets of α-glucosidase. Especially, 5e and 5j showed similar interaction pattern, as previously reported Casuarine-enzyme complex. In vitro analysis suggests that compounds 5a-5k showed varying degrees of α-amylase and α-glucosidase inhibitory activity. Amongst them, 5e and 5j demonstrated good enzyme inhibition while remaining compounds showed low to moderate inhibitory potential. Conclusions Addition of 2,5 dimethoxy substituent (2,5-dimethoxybenzaldehyde) (5e) or hydroxy, methoxy substituents (6-methoxy-2-naphthol aldehyde) (5j) at ortho and meta position exhibited good α-amylase and α-glucosidase inhibition. Hence this study provides several insights on improving the pharmacological profile of triazole containing compounds that can be adopted to design and develop novel glucosidase inhibitors.

The antibacterial target, enoyl-acyl carrier protein (ACP) reductase, is a homotetrameric enzyme that catalyzes the last reductive step of fatty acid biosynthesis. In the present paper, Surflex docking has been carried out on a series (10 compounds) of enoyl ACP reductase inhibitors, using the SYBYL-X 2.0 package (Tripos Inc., St. Louis, USA). Surflex-docking studies revealed that the carbonyl group and pyrazole ring were significant for binding to the receptor, and it is also found that the pattern of binding of tested compounds is same as that of the 4TZK ligand, this in turn helped in understanding of specific activity of compounds.

A series of novel acridine-thiazole bridged coumarin derivatives 3a–3i were designed, synthesized and subjected for their in-vitro antiproliferative activity on human breast cancer (MDA-MB-231), lu...

Novel N,4-diphenylthiazol-2-amine derivatives were designed and synthesized employing Hantzsch method. The three-step reaction involved in the synthesis occurred at a faster rate with excellent yields in eco-friendly conditions. The synthesized derivatives were characterized by spectral techniques such as 1H NMR, 13C NMR, FT-IR and GCMS. Single-crystal X-ray diffraction studies also confirmed the formation of title compounds. These compounds were evaluated in vitro for their antimicrobial and anti-inflammatory activities. The results demonstrated that most of the tested compounds showed potent antifungal activity. Interestingly, these compounds also exhibited good anti-inflammatory and moderate antibacterial activity towards sensitive as well as resistant bacterial strains. In silico studies depicted their good binding affinity profile against S. aureus (PDB ID: 1AD4) and C. albicans (PDB ID: 1AI9).

Since 2019, the infection of SARS‐CoV‐2 has been spreading worldwide and caused potentially lethal health problems. In view of this, the present study explores the most commodious and environmentally benign synthetic protocol for the synthesis of tetrahydrobenzo[b]pyran and pyrano[2,3‐d]pyrimidinones as SARS‐CoV‐2 inhibitors via three‐component cycloaddition of aromatic aldehyde, malononitrile, and dimedone/barbituric acid in water. Lemon peel from juice factory waste, namely, lemon ( Citrus limon ), sweet lemon ( C. limetta ), and Kaffir lime or Citron ( C. hystrix ), effectually utilized to obtain WELPSA, WESLPSA, and WEKLPSA, respectively, for the synthesis of title compounds. The catalyst was characterized by scanning electron microscope (SEM) and energy‐dispersive x‐ray spectroscopy (EDX). The concentration of sodium, potassium, calcium, and magnesium in the catalyst (WELPSA) was determined using atomic absorption spectrometry (AAS). The current approach manifests numerous notable advantages that include ease of preparation, handling and benignity of the catalyst, low cost, green reaction conditions, facile workup, excellent yields (93%–97%) with extreme purity, and recyclability of the catalyst. Compounds were docked on the crystal structure of SARS‐CoV‐2 (PDB: 6M3M). The consensus score obtained in the range 2.47–4.63 suggests that docking study was optimistic indicating the summary of all forces of interaction between ligands and the protein., Since 2019, the infection of SARS‐CoV‐2 has been spreading worldwide and caused potentially lethal health problems. In view of this, the present study explores the most commodious and environmentally benign synthetic protocol for the synthesis of tetrahydrobenzo[b]pyran and pyrano[2,3‐d]pyrimidinones as SARS‐CoV‐2 inhibitors via three‐component cycloaddition of aromatic aldehyde, malononitrile, and dimedone/barbituric acid in water. The use of green catalyst WELPSA obtained from the agricultural wastes is the major addition to this protocol.

β-Secretase (BACE1) has been broadly documented as one of the possible therapeutic targets for the treatment of Alzheimer's disease. In this paper, we report the synthesis and the for β-secretase (BACE-1) inhibitory activity of new series of tetrahydrobenzo [b] pyran derivatives. One-pot synthesis of tetrahydrobenzo [b] pyrans was carried out by condensing aromatic aldehyde, malononitrile and 1,3-cyclohexanedione using ionic liquid 1-butyl-3-methyl imidazolium chloride ([bmIm]Cl-) in aqueous alcohol media. The addition of alcohol and water in the ratio of 1:2 keeps all the reactants in solution which facilitates the reaction and makes the product formation very easy. The synthesized compounds were subjected to BACE1 inhibition assay and six compounds, 4d, 4e, 4f, 4h, 4i, and 4p have shown significant IC50 values at micromolar level. Among these six active compounds, 4e was a potential inhibitor with its IC50 value in nanomolar range. All the synthesized compounds were docked onto the active site of β-Secretase enzyme.

Purpose: To investigate N-succinyl chitosan nanoparticles (NSC NPs) encapsulation with Dunaliella bardawil (D. bardawil) biomass for high utilization enhanced effectiveness and least side effects for anticancer activity. Methods: The potential bioactive compounds from D. bardawil biomass were encapsulated NSC NPs by ionotropic gelation method and to characterize its molecular shape, particle size, stability and polydispersity index using FTIR, XRD, SEM, TEM and Zetasize Nano analyzer. Signaling pathway analysis, molecular docking study and in vitro anticancer screening were performed on chosen H-Ras P21, 721P and liver cancer cell lines (HepG2), respectively. Results: The D. bardawil biomass majorly contains 6 bioactive compounds such as β-carotene, lutein, zeaxanthin, phytoene, canthaxanthin, and phytofluene were identified by LC-MS. The D. bardawil biomass encapsulated NSC NPs showed an average particle size of 80±5.6 nm in spherical shape, crystalline nature, zeta potential of -32±2.7 mV and polydispersity index of 0.51±0.02. Interestingly, the identified target using graph theoretical signaling pathway analysis and molecular docking study showed strong interaction of NSC NPs in binding pockets of H-Ras P21 protooncogene. At 50μg/mL, NPs displayed 95.60% cytotoxicity in HepG2 cell line. The apoptotic cell cycle analysis showed cell death for 24 h and 48 h representing 13.13% and 47.04%, respectively. Conclusion: The highly cross-linked, biocompatible, biodegradable, nontoxic NSC NPs promising carrier for delivery of bioactive molecules present in the D. bardawil biomass was found to be actively involved in deregulation of cellular growth in targeted cancer cells. Thus active NPs serve as a novel nanodrug to enhance the controlled; site specific drug delivery in the management of cancer.

Hit, Lead & Candidate Discovery A variety of novel 2-(methyl/phenyl)-3-(4-(5-substituted-1,3,4-oxadiazol-2-yl)phenyl) quinazolin-4(3H)-ones have been synthesized by treating 3-(4-(5-mercapto-1,3,4-oxadiazol-2-yl)phenyl)-2-(methyl/phenyl)-quinazolin-4(3H)-one with a variety of secondary amines. Graph theoretical analysis was used in identification of drug target that is, NMDAR (N-methyl-d-aspartate receptors). The observed reports of in silico modeling and ligand based toxicity, metabolism prediction studies were encouraging us to synthesize of title compounds and evaluate their antiepileptic effects. The title compounds were tested for its antiepileptic potency by MES and scPTZ model. Rotorod test is used to assess its neurotoxicity. In the preliminary test it was found that in MES test, analogs 6d, 6e, 6f, and 6l were potent; whereas in scPTZ test analogs 6d, 6e, 6f, and 6k displayed potent antiepileptic activity. Additionally these five derivatives were tested in rats orally at a dose of 30 mg/kg and found that compounds 2-methyl-3-(4-(5-morpholino-1,3,4-oxadiazol-2-yl)phenyl)quinazolin-4(3H)-one 6e and 2-methyl-3-(4-(5-(piperidin-1-yl)-1,3,4-oxadiazol-2-yl)phenyl)quinazolin-4(3H)-one 6f exhibited superior activity than reference Phenytoin. In MES test, these derivatives 6e and 6f showed activity at 30 mg/kg i.p. dose after 0.5 hr and 4.0 hr. In scPTZ test these derivatives 6e and 6f showed activity at 100 and 300 mg/kg i.p. dose after 0.5 hr and 4.0 hr, respectively.

We report a series of C N bridged coumarin-thiazolidine-2,4-dione derivatives 3(a–q). These compounds have been synthesized under both conventional as well as microwave irradiation techniques. The synthesized compounds were characterized by spectral and elemental analyses. The computational study performed for targeted compounds and results obtained were mimicking the potent bio-molecules. All the newly synthesized compounds were screened for their in vitro anti-microbial and anti-inflammatory activities and have shown promising results. In vitro Anti-microbial activity of compounds (3a) and (3i) was found to be most active with bacterial and fungal strains. The compound (3i) shows best anti-inflammatory activity with IC50 of 43.26 µg/mL against protein denaturation.

A series of novel quinoline-2-carboxamides 4(a–l) were synthesized using different 2-oxo-2H-chromene-4-carbaldehyde and 3-methyl-1H-pyrazole-5(4H)-one with excellent yield under eco-friendly condition. All the compounds were confirmed on the basis of their IR, 1H NMR, 13C NMR and mass analysis. Newly synthesized compounds were screened for their anti-inflammatory by using protein denaturation method and anticancer activities at NCI60, Anti-inflammatory results are found to be promising. Further, molecular docking studies were performed for all the synthesized compounds with the active site of COX-2 enzyme and results obtained are quite promising. Compounds 4e and 4h exhibited highest potency and selectivity for COX-2 inhibitory activity.

In an effort to produce new lead antimycobacterial compounds, herein we have reported the synthesis of a sequence of new pyrrolyl benzamide derivatives. The new chemical entities were screened to target enoyl-ACP reductase enzyme, which is one of the key enzymes of M. tuberculosis that are involved in type II fatty acid biosynthetic pathway. Compound 3q exhibited H-bonding interactions with Tyr158, Thr196 and co-factor NAD+ that binds the active site of InhA. All the pyrrolyl benzamide compounds were evaluated as inhibitors of M. tuberculosis H37Rv as well as inhibitors of InhA. Among them, few representative compounds were tested for mammalian cell toxicity on the human lung cancer cell-line (A549) and MV cell line that presented no cytotoxicity. Five of these compounds exhibited a good activity against InhA.

A modest, competent and green synthetic procedure for novel coumarinyl-1,3,4-oxadiazolyl-2-mercaptobenzoxazoles 8i-t has been reported. Analysis of the docked (PDB ID: 5IKR; A-Chain) poses of the compounds illustrated that they adopt identical conformations to the extremely selective COX-2 inhibitor. The biological outcomes as well as computational study suggested that the compounds originated to have elevated resemblance towards COX-2 enzyme than COX-1. The compounds 8i, 8l, 8q, 8r, 8s and 8t emerged as most potent and selective COX-2 inhibitors in contrast with Mefenamic acid. The selectivity index of 8l, 8n and 8r was respectively found to be 33.95, 20.25 and 24.98 which manifested their high selectivity against COX-2. Interestingly, the compounds which were active as COX-2 inhibitors were also active as antioxidant agents.

Background A hybrid molecule of different biologically active substances can improve affinity and efficiency compared to a standard drug. Hence based on this fact, we predict that a combination of fluorine, oxadiazole, sulfur, etc., may enhance α-glucosidase inhibition activity compared to a standard drug. Methods A series of novel 5-(2,5-bis(2,2,2-trifluoroethoxy)phenyl)-1,3,4-oxadiazole-2-thiol derivatives (2a-2i) were synthesized and characterized using spectroscopic techniques such as 1HNMR and LC-MS. In order to evaluate its bioactivity, in vitro α-amylase and α-glycosidase inhibitory activity were performed. In vivo study was carried using a genetic model, Drosophila melanogaster, for assessing the antihyperglycemic effects. Results The compounds 2a-2i demonstrated α-amylase inhibitory activity in the range of IC50 = 40.00–80.00 μg/ml as compare to standard acarbose (IC50 = 34.71 μg/ml). Compounds 2a-2i demonstrated α-glucosidase inhibitory activity in the range of IC50 = 46.01–81.65 μg/ml as compared to standard acarbose (IC50 = 34.72 μg/ml). Docking studies on a target protein, N-terminal subunit of human Maltase-glucoamylase (PDB:2QMJ) was carried and the compounds were found to dock into the active site of the enzyme (Fig. 1). The predicted binding energies of the compounds were calculated. The in vitro studies indicate that compounds 2b and 2g had better activity among the synthesized compounds. Whereas in vivo study indicates that 2b, 2g, and 2i could lower glucose levels in the Drosophila, but then 17–30% reduced capacity than acarbose and may be overcome by adjusting their dosage. Conclusions The in vitro and in vivo studies indicate that compounds 2b and 2g had better activity among the synthesized compounds. This study has recognized that compounds like 2b, 2g, and 2i may be considered potential candidates for further developing a novel class of antidiabetic agents.

Quinolin-3-yl-methyl-1,2,3-triazolyl-1,2,4-triazol-3(4H)-ones 8j-v were synthesized by click chemistry as an ultimate tactic where [3 + 2] cycloaddition of azides with terminal alkynes has been evolved. Herein, we are inclined to divulge the implication and prevalence of CuSO4·5H2O and THF/water promoted [3 + 2] cycloaddition reactions. The foremost supremacy of this method are transitory reaction times, facile workup, excellent yields (88–92%) with exorbitant purity and regioselective single product formation both under conventional and microwave method. Docking studies illustrated strong binding interactions with enzyme InhA-D148G (PDB ID: 4DQU) by means of high C-score values. The anti-tubercular and antifungal screening of synthesized compounds proclaimed promising activity. The in vitro and in silico studies imply that these triazoles appended quinolines may acquire the ideal structural prerequisites for auxiliary expansion of novel therapeutic agents.

For this work, two series of new piperazine derivatives (3a-o) and triazolo-pyrazine derivatives (3p-t) were synthesized in a single-step reaction. All twenty adducts were obtained in good to high yields and fully characterized by

A series of novel alkyl substituted purines were synthesized. 6-[4-(4-Propoxyphenyl)piperazin-1-yl]-9H-purine was used as the key starting material, which was synthesized via a multistep protocol and finally subjected for N-alkylation with various alkyl halides with an aim to get prospective antimicrobial agents. The structures of the novel compounds were established by substantiating them through spectral techniques like 1 H-NMR, 13 C-NMR, FT-IR and EI-MS. They were explored for antitubercular activity against Mycobacterium tuberculosis H37RV. Furthermore, they were checked for their antimicrobial activity concerning bacterial and fungal strains. The title compounds exhibited considerable antimicrobial activity without any significant toxicity. In silico studies depicted their good binding profile against Mycobacterium tuberculosis enoyl reductase (InhA; PDB ID: 4TZK) and Candida albicans dihydrofolate reductase (PDB ID: 1AI9). The title compounds obeyed Lipinski's parameters and have exhibited good drug-like properties.