Compounds 4i Research Articles

A one-pot microwave green synthesis of pyrrolo[1,2-c]imidazole-1-one analogs and structural studies

An efficient green method developed as a one-pot synthesis of pyrrolo[1,2-c]imidazole-1-one derivatives under microwave conditions via two-component using a substoichiometric quantity of water. The conformational and structural studies were conducted through DFT optimization and single-crystal X-ray diffraction. The molecular packing was mediated through hydrogen bonding and C-H...π interactions. The Hirshfeld surface analysis highlighted significant H-H interactions in all compounds, with compound 2a exhibiting the highest percentage. HOMO and LUMO studies revealed compound 2a as more stable and less reactive. The molecular electrostatic potential provided the charged proportionality along with the molecular surface. The drug-likeness properties suggested that compounds 2b, 2c, 2d, 2e, 2f, 2g, and 2i possess favorable properties for potential pharmaceutical applications.

Novel Chalcone Derivatives Containing Pyridone and Thiazole Moieties: Design, Synthesis, Molecular Docking, Antibacterial, and Antioxidant Activities

Abstract: A new series of chalcones 4a-i; 6a,b, and 8 was synthesized from the condensation of ketone 2, which was prepared from the reaction of thiourea derivative 1 with 3- chloropentane-2,4-dione in MeOH at reflux temperature, with substituted aromatic/ heterocycle aldehydes in EtOH containing NaOH at room temperature. Antimicrobial and antioxidant activities were assessed for the synthesized compounds. The antimicrobial susceptibility tests revealed that compounds (4c, 4e, 4f, and 4i) exhibited good to excellent activity against C. albicans, S. aureus ATCC25923, E. faecalis ATCC29212, P. aeruginosa ATCC10145, and S. mutans ATCC25175. The antioxidant capabilities were assessed using the DPPH and ABTS radical scavenging methods. Compounds (4b, 4c, 4d, and 4e) proved to be better at scavenging DPPH and ABTS. This study involved in-silico drug-likeness and physicochemical properties and evaluated their ADMET profiles. According to the results of the molecular docking simulation, the synthesized compounds showed lower binding energy at the active sites of Dihydropteroate synthase, Sortase A, LasR, and Penicillin-binding protein pockets, which suggests that they may have an inhibitory effect on the enzymes and show promise as antimicrobial agents.

Synthesis of novel pyrimido[4,5-b]quinoline derivatives as dual EGFR/HER2 inhibitors as anticancer agents.

A series of novel N-aryl-5-aryl-6,7,8,9-tetrahydropyrimido[4,5-b]quinolin-4-amines 4a-4l was synthesized as potential anticancer agents through Dimroth rearrangement reaction of intermediates 3a-3c. Pyrimido[4,5-b]quinolines 4a-4l showed promising activity against the Michigan Cancer Foundation-7 (MCF-7) cell line, compared with lapatinib as the reference drug. Compounds 4d, 4h, 4i, and 4l demonstrated higher cytotoxic activity than lapatinib, with IC50 values of 2.67, 6.82, 4.31, and 1.62 µM, respectively. Compounds 4d, 4i, and 4l showed promising epidermal growth factor receptor (EGFR) inhibition with IC50 values of 0.065, 0.116, and 0.052 µM, respectively. These compounds were subjected to human epidermal growth factor receptor 2 (HER2) inhibition and showed IC50 values of 0.09, 0.164, and 0.055 µM, respectively. Compounds 4d, 4i, and 4l are good candidates as dual EGFR/HER2 inhibitors. The most active compound, 4l, was subjected to cell-cycle analysis and induced cell-cycle arrest at the S phase. Compound 4l induced apoptosis 60-fold compared with control untreated MCF-7 cells. 4l can inhibit cancer metastasis. It reduced MCF-7 cell infiltration and metastasis by 45% compared with control untreated cells.

Mesomorphic, magnetic and DFT studies of biphenyl-based molecule with various substituted anilines

ABSTRACT A new series of liquid crystals consisting of biphenyl unit connected to phenyl core system have been successfully prepared wherein various substituents X= OCH3, F, Cl, Br and I were introduced in the para position of the imine fragment while the length of terminal alkoxy chain of seven carbon atoms was intact. The mesomorphic and thermal studies by POM and DSC exhibit dominant enantiotropic nematic (N) phase. A relatively weak magnetism was detected with vibrating sample magnetometer (VSM) for compounds 3F and 3I at room temperature, wherein the magnetic strength of fluoro-substituted compound appeared stronger than the iodo-substituted compound. The connectivity between the substituents X and their kinetic stability associated with the changes in HOMO-LUMO energy gap value (ΔEgap) supports that the terminal substituents X have great influence on the ΔEgap which can be ascribed to the chemical activity of the compounds. Present study shows an increase in the ΔEgap from OCH 3 < I < Br < Cl < F, where the largest ΔEgap indicates high molecular kinetic stability and low chemical reactivity because adding electrons to high-lying LUMO is energetically unfavourable, resulting in disruption of the molecular packing and reduction of nematogenic, which were validated by DSC and POM.

Rational synthesis and evaluation of 2,4-diamino-thieno[2,3-d]pyrimidines as antitumor agents

Based on structure-guided of thieno[2,3-d]pyrimidine skelecton functionalities and computer-aided drug development strategy, a series of novel 2,4-diamino-thieno[2,3-d]pyrimidine derivatives were designed and synthesized, and their structure confirmed by 1H NMR, 13C NMR and HR-MS. All synthesized compounds were evaluated for antitumor activities against hepatic carcinoma (HepG2) cell lines in vitro, and results showed that all the target compounds exhibited potent antitumor activity. Preliminary comparison indicated that a more bulky substituent group at the C-4 position, and at the same time the introduction of 3-Cl on the phenyl ring with 4-methyl group on the C-2 position of thieno[2,3-d]pyrimidine have remarkable influence on activity. One of the expected target compound 5i showed the best inhibition activities against HepG2 with IC50 value 0.17 μmol/L. To further investigate the structure-activity relationship, the docking experiment of 5i, 5j, 5o and Gefitinib on EGFR were performed. The docking results displayed that compound 5i was able to be tightly embedded in the active pocket of EGFR and the binding energy is most negative with EGFR, which demonstrating that compound 5i can be take a potential lead compound for further lucubrate.

Synthesis of Some New 1,3,4-Oxadiazole Derivatives and Evaluation of Their Anticancer Activity.

In this work, some new 2-[(5-((2-acetamidophenoxy)methyl)-1,3,4-oxadiazol-2-yl)thio]acetamide derivatives (4a-4l) were synthesized and studied for their anticancer activity. Twelve new compounds were tested on the A549 human lung cancer cell line, C6 rat glioma cell line, and L929 murine fibroblast cell line. Compounds 4f, 4i, 4k, and 4l (IC50: 1.59-7.48 μM), and especially 4h (IC50: <0.14 μM), exhibited excellent cytotoxic profile on A549 with selectivity. Compounds 4g and 4h showed remarkable antiproliferative activity on the C6 cell line with IC50 values of 8.16 and 13.04 μM, respectively. The compounds with the lowest IC50 value on the A549 cell line (4f, 4h, 4i, 4k, and 4l) were further studied to determine the mechanism of action. These compounds were found to induce apoptosis with a higher ratio (16.10-21.54%) than that of the standard drug cisplatin (10.07%). Compound 4f displayed mitochondrial membrane depolarization and caspase-3 activation at most, whereas compounds 4h (89.66%) and 4i (78.78%) had outstanding retention rates in the G0/G1phase of the cell cycle (cisplatin 74.75%). Compounds 4f, 4g, 4h, and 4l exhibited matrix metalloproteinase-9 (MMP-9) inhibition higher than 75% at 100 μg/mL; even IC50 values were found to be 1.65 and 2.55 μM for 4h and 4l. In addition, in silico physicochemical properties of the compounds and molecular docking interaction of compound 4h on the MMP-9 enzyme were evaluated; the desired and expected results were obtained.

1,3,4-oxadiazole derivatives: synthesis, characterization, antifungal activity, DNA binding investigations, TD-DFT calculations, and molecular modelling

1,3,4-Oxadiazole-based heterocyclic analogs (3a–3m) were synthesized via cyclization of Schiff bases with substituted aldehydes in the presence of bromine and acetic acid. The structural clarification of synthesized molecules was carried out with various spectroscopic techniques such as FT-IR,1H and 13C-NMR, UV–visible spectroscopy, and mass spectrometry. In-vitro antifungal activity was performed against C. albicans, C. glabrata and C. tropicalis and analogs 3g, 3i, and 3m showed potent MIC at 200 µg/ml and excellent ZOI measurements of 17–21 nm. The cell viability on Huh7 for lead molecules 3g, 3i, and 3m was found to be 99.5%, 92.3%, and 86.9% at 20, 10, and 20 μM, respectively. The antioxidant activity of molecules 3 g, 3i, and 3 m was estimated and exhibited great IC50 values of 0.104 ± 0.021, 0.145 ± 0.05, and 0.165 ± 0.018 μg/mL with DPPH and 0.107 ± 0.04, 0.191 ± 0.12, and 0.106 ± 0.08 with H2O2, respectively. The binding interaction mode for the lead molecules was also carried out with Ct-DNA using the absorption, emission, CV, CD, and Time resolve fluorescence techniques. The results showed good binding constant (Kb) values of 9.1 × 105, 9.94 × 105, and 9.32 × 105 M−1 for 3g, 3i, and 3m, respectively. TD-DFT study of compounds 3g, 3i, and 3m was done to find out HOMO/LUMO energy levels, surface study of the molecular electrostatic potential, Mulliken population analysis, and natural bond orbitals showing the linkages between the donors and acceptors.Molecular docking of three lead analogs with PDB ID: 1BNA and molecular modelling of compounds 3g, 3i, and 3m with C. albicans CYP51 protein (PDB ID: 5FSA) were carried out. Communicated by Ramaswamy H. Sarma

Synthesis of nitro‐containing isoquinoline‐1,3‐diones with tert‐butyl nitrite

AbstractAn efficient synthetic method for the nitro‐containing isoquinoline‐1,3‐diones has been achieved with tert‐butyl nitrite. This reaction features metal‐free, safety, simple operation and mild reaction conditions, which represents the first example of using stable and safe tert‐butyl nitrite as the nitro precursor for the synthesis of nitro‐containing isoquinoline‐1,3‐diones. Furthermore, both the control experiments and density functional theory calculations (DFT) have confirmed that the reaction was occurred through the radical reactions. In addition, the representative compounds 3a and 3i displayed potential good inhibitory activities for the plant height of rape and the compound 3a displayed potential promotion activity of the root length for barnyard grass.

Novel indolinone-tethered benzothiophenes as anti-tubercular agents against MDR/XDR M. tuberculosis: Design, synthesis, biological evaluation and in vivo pharmacokinetic study

Joining the global effort to eradicate tuberculosis, one of the deadliest infectious killers in the world, we disclose in this paper the design and synthesis of new indolinone-tethered benzothiophene hybrids 6a-i and 7a-i as potential anti-tubercular agents. The MICs were determined in vitro for the synthesized compounds against the sensitive M. tuberculosis strain ATCC 25177. Potent compounds 6b, 6d, 6f, 6h, 7a, 7b, 7d, 7f, 7h and 7i were furtherly assessed versus resistant MDR-TB and XDR-TB. Structure activity relationship investigation of the synthesized compounds was illustrated, accordingly. Superlative potency was unveiled for compound 6h (MIC = 0.48, 1.95 and 7.81 µg/mL for ATCC 25177 sensitive TB strain, resistant MDR-TB and XDR-TB, respectively). Moreover, validated in vivo pharmacokinetic study was performed for the most potent derivative 6h revealing superior pharmacokinetic profile over the reference drug. For further exploration of the anti-tubercular mechanism of action, molecular docking was carried out for the former compound in DprE1 active site as one of the important biological targets of TB. The binding mode and the docking score uncovered exceptional binding when compared to the co-crystallized ligand suggesting that it maybe the underlying target for its outstanding anti-tubercular potency.

“Design, synthesis, biological profile and molecular modeling and MD simulation studies of heterocyclic benzimidazole and thiazolidine-4-one based 5-arylidene analogues as prospective antimicrobial agents”

A series of benzimidazole-thiazolidine-4-one based 5-arylidene hybrids (5a-5o) were synthesized by condensation of 3-((1H-benzo[d]imidazol-2-yl)methyl)-2-(4-nitrophenyl)thiazolidin-4-one (4) and derivatives of benzaldehyde in ethanol (99 %) using sodium ethoxide as a catalytic agent. Structural elucidation of all the synthesized compounds were performed with IR, 1H NMR, 13C NMR, and mass spectrometry. In vitro antimicrobial activity of the title compounds were evaluated against several bacterial and fungal strains. In comparison to standard drugs, compounds 5b, 5d, 5e, and 5g showed significant antibacterial activity, whereas compounds 5b, 5e, and 5i showed excellent antifungal action, according to their biological activity. In addition, molecular docking and molecular dynamics simulations were performed to ascertain the most stable conformation of newly synthesized inhibitors and to evaluate the stability of molecular interactions within E. coli DNA GyrB protein. Over the course of a 100 nanosecond simulation, compound 5g demonstrated a remarkable degree of stability in its interaction with E. coli DNA GyrB protein. These computational insights unveiled the underlying mechanisms governing antibacterial activity, offering a more comprehensive understanding of the compounds' potential for therapeutic use against bacterial infections.

Hydrazone-sulfonate hybrids as potential cholinesterase inhibitors: design, synthesis and molecular modeling simulation.

Aim: Design and synthesis of a series of hydrazone-sulfonate hybrids, 5a-r. Methodology: The inhibitory properties of the synthesized compounds against acetylcholinesterase and butyrylcholinesterase were evaluated using donepezil as the reference standard. Results & conclusion: Compound 5e was identified as the most potent inhibitor of acetylcholinesterase (IC50=9.30μM), and compound 5i was the most potent inhibitor of butyrylcholinesterase (IC50=11.82μM). To confirm the safety of the most potent hits at the used doses, toxicological bioassays were conducted. Molecular docking was performed and the tested derivatives were found to fit well in the active sites of both enzymes. This study provides valuable insights into the potential of hydrazone-sulfonate hybrids as drug candidates.

Design, synthesis and antitubercular assessment of 1, 2, 3-triazole incorporated thiazolylcarboxylate derivatives

A library of 1, 2, 3-triazole incorporated thiazolylcarboxylate derivatives (7a-q) and (8a-j) were synthesized and evaluated for their in-vitro antitubercular activity against Mycobacterium tuberculosis H37Rv. The two compounds 7h and 8h have displayed excellent antitubercular activity with MIC values of 3.12 and 1.56 µg/mL respectively (MIC values of standard drugs; Ciprofloxacin 1.56 μg/mL & Ethambutol 3.12 μg/mL). Whereas, the four compounds 7i, 7n, 7p and 8i displayed noticeable antitubercular activity with a MIC value of 6.25 µg/mL. The active compounds of the series were further studied for their cytotoxicity against RAW264.7 cell line using MTT assay. Furthermore, to study the probable mechanism of antitubercular action, physicochemical property profiling, DFT calculation and molecular docking study were executed on mycobacterial cell wall target Decaprenylphosphoryl-β-d-ribose 2′-epimerase 1 (DprE1). Among all the compounds, 7h (-10 kcal/mol) and 8h (-10.1 kcal/mol) exerted the highest negative binding affinity against the targeted DprE1 (PDB: 4NCR) protein.

Isoxazole analogues of dibenzazepine as possible leads against ulcers and skin disease: In vitro and in silico exploration

Utilizing multi-target drugs shows great promise as an effective strategy against polygenic diseases characterized by intricate patho-mechanisms, such as ulcers, skin dermatitis, and cancers. The current research centers around the creation of hybrid compounds, connecting dibenzazepine and isoxazole, with the aim of exploring their potential as inhibitors for urease and tyrosinase enzymes. Analogs 6a, 6b, 6d, 6 h-6j, and 6 l demonstrated strong inhibitory potential against tyrosinase enzyme with IC50 values of 4.32 ± 0.31–12.36 ± 0.48. Whereas analogs 6a, 6c, 6e, 6f, 6h-6m, and 6r exhibited potent inhibitory activities against urease enzyme with IC50 values of 3.67 ± 0.91–15.60 ± 0.18 μM. Furthermore, compounds 6i, 6n, and 6r showed weak toxic effect in BJ-cell line, whereas the remaining compounds were found non-toxic to normal cell line. The mechanistic studies of potent inhibitors of both the enzymes showed competitive mode of inhibition. Molecular docking was employed to establish the relationship between structure and activity and to elucidate the interaction mechanism. This analysis revealed that the active analogs exhibited crucial interactions with the active site residues of urease and tyrosinase, thus corroborating our experimental results. Hence, the generated derivatives of dibenzazepine-linked isoxazoles present intriguing starting points for further investigations into their potential as inhibitors of urease and tyrosinase, with the potential for future modification and enhancement.

Discovery of SARS-CoV-2 Inhibitors Featuring Novel Histidine α-Nitrile Motif.

As COVID-19 infection caused severe public health concerns recently, the development of novel antivirals has become the need of the hour. Main protease (Mpro ) has been an attractive target for antiviral drugs since it plays a vital role in polyprotein processing and virus maturation. Herein we report the discovery of a novel class of inhibitors against the SARS-CoV-2, bearing histidine α-nitrile motif embedded on a simple dipeptide framework. In-vitro and in-silico studies revealed that the histidine α-nitrile motif envisioned to target the Mpro contributes to the inhibitory activity. Among a series of dipeptides synthesized featuring this novel structural motif, some dipeptides displayed strong viral reduction (EC50 =0.48 μM) with a high selectivity index, SI>454.54. These compounds also exhibit strong binding energies in the range of -28.7 to -34.2 Kcal/mol. The simple dipeptide structural framework, amenable to quick structural variations, coupled with ease of synthesis from readily available commercial starting materials are the major attractive features of this novel class of SARS-CoV-2 inhibitors. The histidine α-nitrile dipeptides raise the hope of discovering potent drug candidates based on this motif to fight the dreaded SARS-CoV-2.

Design, synthesis docking and molecular dynamics studies of 2-amino-4-phenylthiazole-indole hybrids as α-glucosidase inhibitors

In our effort directed toward the development of novel α-glucosidase inhibitors by molecular hybridization theory, a novel series of 2-amino-4-phenylthiazole-indole hybrids 7a-l was designed, synthesized, and evaluated. Our in vitro results demonstrated that all these compounds (7a-l) were more potent than positive control acarbose. Kinetic study of the most active entry (compound 7i) was also carried out to determine the mode of inhibition. The latter study revealed that compound 7i was a competitive inhibitor against α-glucosidase. Furthermore, the binding interaction modes of the most active compounds within the α-glucosidase active site were studied by molecular docking. Moreover, molecular dynamics of compound 7i was also carried out in order to determine the stability of complex compound 7i-α-glucosidase. The in silico pharmacokinetics and toxicity studies of the most potent compounds predicted that these compounds can be consider as useful lead structures to obtain new anti-diabetic agents.

Multi-step Synthesis of Novel Pyrazole Derivatives as Anticancer Agents

The attractiveness of pyrazole and its derivatives is increasing because of their numerous potential pharmacological applications. A novel series of pyrazole hybrid compounds (6A–6L) has been synthesized, and all the intermediates and the final products were characterized by 1H NMR, IR, and mass spectrometry. Pyrazole derivatives were screened for their anticancer activity against the NCI-60 cell lines, and grouped into nine different subpanels. In-vitro anticancer studies of the targeted compounds showed that the compounds 6C, 6D, 6F, 6I, and 6J showed potent anticancer activity against renal cancer, ovarian cancer, melanoma, and leukemia cancer.

Sonochemical replacement of C-3 hydrogen of indole by a pyridine ring: Docking, synthesis and in vitro evaluation of 3-(6-aryl pyridin-2-yl)indoles against SIRT1

As an emerging pharmacological target for cancer, SIRT1 attracted our attention while searching unique approaches or strategies for the identification of new anticancer agents. Accordingly, the 3-(6-aryl pyridin-2-yl)indole framework was pursued for the design of new and possible inhibitors of SIRT1. Initially, the in silico docking of a number of molecules based on this framework was conducted that showed their promising interactions with SIRT1 in addition to probable selectivity towards this protein over SIRT2. The study also suggested VAL412, PHE414, ILE347, ALA262, ILE411, HIS363, GLN345, ASN346, ILE270, ILE316, PHE273 and PHE297 as the common interacting residues. A majority of compounds participated in non-H bonding interactions through their aromatic rings with the hydrophobic active site pocket of hSIRT1. A convenient access to these 3-(6-aryl pyridin-2-yl)indoles (3) was established via the first ultrasound assisted heteroarylation approach involving a CC bond forming reaction between 6-aryl substituted 2-chloropyridine and indoles in the presence of AlCl3. Indeed, the current approach revealed sonochemical replacement of the C-3 hydrogen of indole by the pyridine ring in a regioselective manner. The compounds obtained were assessed for their SIRT1 inhibitory potential in vitro. Correlating the outcome of in silico studies the compound 3c, 3d, 3f and 3g were emerged as the best active molecules (with ≥ 70% inhibition) whereas compound 3a, 3e, 3i, 3j and 3o showed good inhibition (> 55%) of SIRT1 at 10 μM. According to the Structure-Activity-Relationship (SAR) the promising SIRT1 inhibitory activities were noted when a OMe or NO2 group was present at C-6 position of the indole ring. Based on IC50 values the order of activity of compounds was found to be 3g > 3f > 3c > 3d when 3g being the most potent seemed to be better than nicotinamide.

Synthesis of Tetracyclic Spirooxindolepyrrolidine-Engrafted Hydantoin Scaffolds: Crystallographic Analysis, Molecular Docking Studies and Evaluation of Their Antimicrobial, Anti-Inflammatory and Analgesic Activities

In a sustained search for novel potential drug candidates with multispectrum therapeutic application, a series of novel spirooxindoles was designed and synthesized via regioselective three-component reaction between isatin derivatives, 2-phenylglycine and diverse arylidene-imidazolidine-2,4-diones (Hydantoins). The suggested stereochemistry was ascertained by an X-ray diffraction study and NMR spectroscopy. The resulting tetracyclic heterocycles were screened for their in vitro and in vivo anti-inflammatory and analgesic activity and for their in vitro antimicrobial potency. In vitro antibacterial screening revealed that several derivatives exhibited remarkable growth inhibition against different targeted microorganisms. All tested compounds showed excellent activity against the Micrococccus luteus strain (93.75 µg/mL ≤ MIC ≤ 375 µg/mL) as compared to the reference drug tetracycline (MIC = 500 µg/mL). Compound 4e bearing a p-chlorophenyl group on the pyrrolidine ring exhibited the greatest antifungal potential toward Candida albicans and Candida krusei (MIC values of 23.43 µg/mL and 46.87 µg/mL, respectively) as compared to Amphotericin B (MIC = 31.25 and 62.50 µg/mL, respectively). The target compounds were also tested in vitro against the lipoxygenase-5 (LOX-5) enzyme. Compounds 4i and 4l showed significant inhibitory activity with IC50 = 1.09 mg/mL and IC50 = 1.01 mg/mL, respectively, more potent than the parent drug, diclofenac sodium (IC50 = 1.19 mg/mL). In addition, in vivo evaluation of anti-inflammatory and analgesic activity of these spirooxindoles were assessed through carrageenan-induced paw edema and acetic acid-induced writhing assays, respectively, revealing promising results. In silico molecular docking and predictive ADMET studies for the more active spirocompounds were also carried out.

Synthesis, Characterization, and in vitro Anti-Inflammatory Activity of Novel Ferrocenyl(Piperazine-1-Yl)Methanone-based Derivatives.

Inflammation is closely related to the occurrence and development of various diseases in the clinical scope. Finding effective anti-inflammatory agents is of great significance for clinical treatment. A series of novel ferrocenyl(piperazine-1-yl)methanone-based sulfamides and carboxamides were synthesized to discover potent anti-inflammatory agents. The compounds were characterized by 1H NMR, 13C NMR, and MS spectra. Compound 5h was further determined by single crystal X-ray diffraction. All the target compounds were screened for anti-inflammatory activity by evaluating the inhibition effect of LPS-induced NO production in RAW264.7 macrophages. The novel compound (4i) is the preliminary anti-inflammatory mechanism detected by western blot. In a multi-stage screening campaign, compound 4i was shortlisted, which exhibited physicochemical properties suitable for human administration. Among them, compound 4i was found to be most potent in inhibiting NO production (IC50 = 7.65 μM) with low toxicity. This compound also exhibited significant inhibition of the production of iNOS and COX-2. Preliminary mechanism studies indicated that compound 4i could inhibit the activation of the LPS-induced TLR4/NF-κB signaling pathway. The promising anti-inflammatory activity of compound 4i compared with the reference drug suggests that this compound may contribute as a lead compound in the search for new potential anti-inflammatory agents.

Synthesis, ADME, Molecular Docking and Biological Evaluation of New 2-Aminobenzothiazloes

Background: In recent years, 2-aminobenzothiazoles were reported as antibacterial, antihelmintic, antitumor, antimalarial, antiviral, analgesic and anti-inflammatory agents. Objectives: The study aimed to explore new potential 2-aminobenzothiazoles as antibacterial and anthelmintic agents. Methods: A favorable two-step method was used for the synthesis of new 2-aminobenzothiazole derivatives (4a-4j) by Schiff base. All synthesized compounds were tested for antibacterial activity using an in vitro cup-plate method and antihelmintic activity by recording in vitro earthworm paralysis and death time. Pharmacokinetics in silico studies were performed to predict the drug performance in the body using the Molinspiration kit. The molecular docking was performed to check the catalytic binding site between the dihydrofolate reductase and synthesized compounds (4a-4j). Results: The compound 4d emerged as the most effective vermifuge and vermicide among all tested compounds. The compounds 4c, 4f, 4g, 4i and 4j were examined as highly potent against grampositive bacteria. The compounds 4b, 4h, and 4i showed maximum inhibition against gramnegative bacteria. In support of antibacterial activity, the compounds 4c and 4j showed good binding orientation in the catalytic binding pocket of the DHFR receptor (PDB ID: 4LAE). These synthesized compounds could have evolved to shape orally active compounds shown in pharmacokinetics in silico studies. Conclusions: The research outcomes showed that explored 2-aminobenzothiazoles have good antibacterial and anthelmintic activity.