Synthesis, DFT and In Silico Anti-COVID Evaluation of Novel Tetrazole Analogues

A new series of 3-aryl/heteroaryl-2-(1H-tetrazol-5-yl) acrylamides have been synthesized through catalyst-free, one-pot cascade reactions, utilizing click chemistry approach and evaluated for their anti-COVID activities against two proteins in silico. The structural properties of the synthesized molecules were evaluated based on DFT calculations. Total energy of the synthesized tetrazole compounds were obtained through computational analysis which indicate the high stability of the synthesized compounds. The Frontier Molecular Orbitals (FMO) and associated energies and molecular electrostatic potential (MEP) surfaces were generated for the compounds. Spectral analysis by DFT gave additional evidence to the structural properties of the synthesized molecules. All tetrazole analogues come under good ADMET data as they followed the standard value for ADMET parameters. Docking studies offered evidence of the molecules displaying excellent biological properties as an anti-Covid drug. Compound 4 g exhibited excellent anti-COVID-19 properties with four hydrogen binding interactions with amino acids GLN 2.486 Å, GLN 2.436 Å, THR 2.186 Å and HSD 2.468 Å with good full-fitness score (–1189.12) and DeltaG (–7.19). Similarly, compound 4d shown potent activity against anti-COVID-19 mutant protein (PDB: 3K7H) with three hydrogen binding interactions, i.e., SER 2.274 Å, GLU 1.758 Å and GLU 1.853 Å with full-fitness score of –786.60) and DeltaG (–6.85). The result of these studies revealed that the compounds have the potential to become lead molecules in the drug discovery process.

Direct One-Pot Synthesis of Propofol from Paracetamol Tablets

The COVID-19 pandemic has affected millions of people in the entire world and caused a shortage of several drugs, including propofol. Therefore, several protocols for propofol synthesis have been published in recent years. Herein, we present a process starting from paracetamol, a very common and abundant active pharmaceutical ingredient. Since the first three steps (Friedel-Crafts double alkylation, acetyl deprotection, and diazotization) are done in acidic media, a one-pot approach was developed. Furthermore, we observed that the extraction of the final product can be simplified by steam-distillation, leading to propofol in 47% isolated yield with high purity. This presented process could be an example of active pharmaceutical ingredient reuse since similar results were observed with commercial paracetamol tablets (with excipients) regardless of expiration date. © 2023 American Chemical Society.

Direct One-Pot Synthesis of Propofol from Paracetamol Tablets

The COVID-19 pandemic has affected millions of people in the entire world and caused a shortage of several drugs, including propofol. Therefore, several protocols for propofol synthesis have been published in recent years. Herein, we present a process starting from paracetamol, a very common and abundant active pharmaceutical ingredient. Since the first three steps (Friedel-Crafts double alkylation, acetyl deprotection, and diazotization) are done in acidic media, a one-pot approach was developed. Furthermore, we observed that the extraction of the final product can be simplified by steam-distillation, leading to propofol in 47% isolated yield with high purity. This presented process could be an example of active pharmaceutical ingredient reuse since similar results were observed with commercial paracetamol tablets (with excipients) regardless of expiration date. © 2023 American Chemical Society.

One-pot synthesis, molecular docking, ADMET, and DFT studies of novel pyrazolines as promising SARS-CoV-2 main protease inhibitors

Pyrazoline and its derivatives have numerous prominent pharmacological effects. Focusing on its anti-viral property, we have designed and synthesized three novel pyrazoline derivatives (A1–A3) through one-pot three components and characterized them using different spectroscopic techniques (FT-IR, 1H NMR, 13C NMR, and UV). These compounds were evaluated against SARS-CoV-2 main protease utilizing in-silico molecular docking studies. The docking results displayed good inhibitory activity of the synthesized compounds. Among them, compound A2 was the most active against targeted protein. The drug-likeness and ADMET properties were predicted to have varied profiles but could still be developed, especially A2. DFT/TD-DFT calculations through B3LYP/6-311G++ level of theory were applied to provide comparable theoretical data along with MEP map and electronic energy gap of HOMO → LUMO. [ FROM AUTHOR] Copyright of Research on Chemical Intermediates is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

Advances in Synthetic Strategies and Medicinal Importance of Benzofurans: A Review

Out of the many heterocycles that exhibit pharmaceutical and therapeutic properties, benzofurans remain the most eye-catching to scientists ever since their discovery. From being present in natural products to synthetic analogs they show diverse biological properties which are used to treat various diseases. Interestingly, some of the benzofuran hybrids were docked against COVID-19 Main Protease and it showed appealing results. Apart from medicinal properties it also exhibits some non-drug applications. The structure activity relationship of benzofuran derivatives in many infections draws attention to the extent where drugs can be produced in a short time span which highlights their significance in medicinal chemistry. There are considerable reaction schemes to synthesize this moiety either simple one pot reactions or multistep. Here, we emphasize on the chemistry of benzofurans, synthesis and its derivatives in the recent years, some of which show notable anti-tumor, anti-fungal, anti-mycobacterial and anti-oxidant activities.

One-Pot Consecutive Reductive Amination Synthesis of Pharmaceuticals: From Biobased Glycolaldehyde to Hydroxychloroquine

Reductive amination plays a paramount role in the synthesis of amines. It is often proposed as a more ecofriendly synthesis process than the traditional SN2-type reactions of amines as it avoids toxic alkylation reagents such as alkyl halides. This work demonstrates the versatility of the reductive amination reaction via the synthesis of hydroxychloroquine (HCQ), one of the most renowned pharmaceuticals during this coronavirus pandemic. The novel green synthesis strategy is based on three consecutive reductive amination reactions conducted in a one-pot system, avoiding intermediary purification steps. Furthermore, a biobased C2 platform molecule, glycolaldehyde, was selected as a starting reagent. The newly developed reductive amination pathway was appraised using the CHEM21 Green Metric toolkit and compared with the commercially operating method. © 2022 American Chemical Society.

New experimental low-cost nanoscience technology for formulation of silver nanoparticles-activated carbon composite as a promising antiviral, biocide, and efficient catalyst

A simple low-cost one-pot photodeposition synthesis with no hazardous reactants or products is used to make silver nanoparticles-activated carbon composite (SNPs@AC). The SNPs are homogenously and photodeposited and absorbed into the activated carbon matrix. Both SNPs and SNPs@AC composite have particle sizes around 10 nm and 100 nm, respectively. The SNPs@AC composite showed good antiviral activity to VERO (ATCC ccl-81) cells. Zeta potential of SNPs@AC composite is −25 mV, showing that this colloidal system is electrically stable and resistant to coagulation. For many Gram-positive and Gram-negative bacteria, the SNPs@AC composite demonstrated strong antibacterial efficacy. The SNPs@AC composite has 75.72 percent anti-inflammatory effect at concentration 500 µg/mL. This composite has a maximum non-toxic concentration (MNTC) of 78.125 g/mL, which corresponds to antiviral activity of up to 96.7 percent against hepatitis A. virus (HAV). It is suggested as a candidate for pharmaceutical formulations, such as integration into the manufacture of N95 masks for COVID-19 infection protection. Concentration 160 μg/mL SNPs@AC composite has antioxidant activity 42.74% percent. The SNPs@AC composite exhibited selective catalytic activity for the organosynthesis hydrazination reaction of 4-chloro-3, 5-di-nitro-benzo-triflouride, giving 1-hydroxy-4-nitro-6-trifluoro-methyl benzotriazole, a common antiviral drug for severe acute respiratory syndrome (SARS). SNPs@composite's well-defined pores provide suitable active sites for binding reactants: 4-Cl-3, 5-di-NO2-benzotriflouride, and hydrazine, which react to create 1-hydroxy-4-nitro-6-trifluoromethyl benzotriazole, which diffuses into solution away from the catalyst surface, leaving the catalyst surface unaffected.

Metal-organic frameworks encapsulated with an anticancer compound as drug delivery system: Synthesis, characterization, antioxidant, anticancer, antibacterial, and molecular docking investigation

Metal organic framework (MOF) hybrid materials could be one of the answers in this investigation. We describe a simple and effective encapsulation of doxorubicin (DOX), an anticancer drug, inside Zr-MOF, which have been little studied as drug delivery organizations. We investigated the measured release of the drug from Zr-MOF in response to external incentives such as pH changes and interaction with biomimetic schemes. Zr-MOF with encapsulated doxorubicin (DOX@Zr-MOF) can be manufactured in one pot by addition the anticancer medication DOX to the reaction combination. They demonstrated pH-responsive medication release and cancer cell killing capability. MOFs can be designed as multifunctional distribution vehicles for a diversity of loads, including medicinal and imaging agents, using our simple one-pot approach. Fourier transform infrared (FTIR), X-ray diffraction, scanning electron microscopy, and N-2 sorption isotherm were used to analyze MOF and the developed drug delivery (DOX@Zr-MOF) scheme. It investigated the effects of MOF and a bespoke drug delivery system on the feasibility of patient breast as well as liver tumor cell lines. At pH 5, the trapped drug can be released more quickly than at pH 7.4. Zr-MOF nanoparticles had modest cytotoxicity;however, DOX@Zr-MOF has higher cytotoxicity in MCF-7 and HepG-2 cells than DOX at concentrations greater than 31.25 mu g ml(-1). These results were discovered that DOX@Zr-MOF could be a promising technique for delivering medicines to cancer cells. Furthermore, using the agar well dispersion technique, Zr-MOF, DOX, and captured DOX@Zr-MOF samples were assessed for their potential antibacterial activity against pathogenic bacteria in comparison to traditional antibiotics. In compared to the reference medication Gentamycin, the DOX@Zr-MOF exhibits a large inhibitory zone against Gram negative organisms (Escherichia coli). The docking active place interactions were assessed to see if DOX might bind to the breast cancer 3hb5-oxidoreductase receptor, prostate cancer protein 2q7k, and SARS-CoV-2 protease 6YB7 for anticancer and anticovid-19 activities.