Compounds 3f Research Articles

Synthesis and biological assessment of novel 4H-chromene-3-carbonitrile derivatives as tyrosinase inhibitors.

Excessive activity of the tyrosinase enzyme during melanogenesis results in hyperpigmentation in the skin. To address this issue, there is a need to develop effective tyrosinase inhibitors as a treatment for hyperpigmentation. In this study, we synthesized some novel 4H-chromene-3-carbonitrile compounds (6a-o) and assessed their inhibitory activities against tyrosinase, comparing them with kojic acid, which is known as a positive control. Compound 6f emerged as the most effective inhibitor, with an IC50 of 35.38 ± 2.12 µM. Kinetic studies of 6f exhibited competitive inhibition, with Ki = 16.15 µM. Molecular docking studies highlighted the importance of π-π stacking and hydrogen bonding interactions within the binding site. Molecular dynamics simulations showed that the R-enantiomer 6f exhibited superior binding stability compared to the S-enantiomer, with a lower standard deviation of RMSD and more persistent interactions with the key active site residues. These findings underscore the potential of the R-enantiomer of compound 6f as a potent tyrosinase inhibitor and provide insights for developing effective treatments for hyperpigmentation and related skin conditions.

In vitro antiplasmodium and antitrypanosomal activities, β-haematin formation inhibition, molecular docking and DFT computational studies of quinoline-urea-benzothiazole hybrids

Quinoline-urea-benzothiazole hybrids exhibited low to sub-micromolar in vitro activities against the Plasmodium falciparum (P. falciparum) 3D7 chloroquine (CQ)-sensitive strain, with compounds 5a, 5b and 5f showing activities ranging from 0.33 to 0.97 μM. Against the formation of β-haematin, the majority of the tested compounds were comparable to the reference drug, chloroquine (CQ), with compounds 5c (IC50 = 9.55 ± 0.62 μM) and 5h (IC50 = 9.73 ± 1.38 μM), exhibiting slightly better in vitro efficacy than CQ. The hybrids also exhibited low micromolar to submicromolar activities against Trypanosoma brucei brucei, with 5j-5k being comparable to the reference drug, pentamidine. Compound 5b displayed higher in silico binding energy than CQ when docked against P. falciparum dihydroorotate dehydrogenase enzyme. Compounds 5j and 5k showed higher binding energies than pentamidine within the trypanothione reductase enzyme binding pocket. The root means square deviations of the hit compounds 5b, 5j and 5k were stable throughout the 100 ns simulation period. Post-molecular dynamics MMGBSA binding free energies showed that the selected hybrids bind spontaneously to the respective enzymes. The DFT investigation revealed that the compounds have regions that can bind to the electropositive and electronegative sites of the proteins.

Design, synthesis, biological evaluation, kinetic studies and molecular modeling of imidazo-isoxazole derivatives targeting both α-amylase and α-glucosidase inhibitors

Herein, a novel set of imidazo-isoxazole derivatives containing thiourea and urea scaffolds were synthesized, characterized (1H NMR, 13C NMR, and elemental analysis). These compounds were biologically evaluated for their α-amylase and α-glucosidase inhibitory activity, identifying 5f as the most active (IC50 26.67 ± 1.25 μM and 39.12 ± 1.83 μM against α-amylase α-glucosidase, respectively), better than the standard, acarbose. Enzymatic kinetic results showed that 5f and acarbose complete competitive type inhibitors. The structure-activity relationship (SAR) demonstrated that undergoing substitutions on R1 and R2 groups attached to the thiourea/urea moiety chains controlled the activity. Besides, in-silico ADMET study showed that almost title compounds exhibited satisfactory pharmacokinetic properties. In molecular docking study, the top performing compound (5f) exhibited higher binding energies (−5.501 and −6.414 kcal/mol, respectively) showing crucial interactions and that snuggly fit in their active site. To shed light on their mechanism of action, molecular dynamic (MD) simulations approach executed at 100 ns duration authenticated the high stability of 5f-1B2Y and 5f-3A4A complexes. The results of this investigation disclosed that compound 5f may serve as a potential lead, accomplished with in vivo studies, for the management of diabetes.

Synthesis, Structural, DFT studies, Biological Effectiveness, and Molecular Docking Aspects of Multitarget Novel N-(4-Phenylthiazol-2-yl)hydrazine carboxamide Hybrids as COX inhibitors, Anti-TB, and Anti-oxidant activity

We herein report, a series of N-(4-phenylthiazol-2-yl)hydrazinecarboxamide based multitarget compounds 3(a-i) were designed and synthesized. Ten compounds 2, and 3(a-i) were characterized by FTIR, NMR (1H and 13C), and mass analysis and subsequently, tested for their potential COX inhibitors, anti-TB, and anti-oxidant activities. The physicochemical and ADME studies for newly synthesized compounds were disclosed. The DFT calculations were taken for the selected molecules using CAM-B3LYP hybrid functional with a 6–31+g(d) all-electron basis set using the Gaussian 09 package. The compounds 3d, 3e, and 3f recognized outstanding COX-II inhibitions with IC50 values of 0.62, 0.78, and 0.72 μM compared to standard drugs. The compounds 3d, 3e, and 3f showed outstanding anti-TB activity with a MIC value of 0.78μg/mL. The compound 3d, and 3f attested outstanding antioxidant activity at 10 μg/mL with a rate of inhibition of 68.12%, and 68.85% respectively. Finally, the molecular docking studies carried out with cyclooxygenase-2 (PDB ID: 6COX), M. tuberculosis enoyl reductase (INHA) (PDB ID: 4TZK), and cytochrome c peroxidase (PDB ID: 2×08), for all the newly synthesized derivatives. Finally, selected compounds were taken for their molecular dynamic studies.

Synthesis, spectroscopic characterization, DFT calculations, in silico-ADMET and molecular docking analysis of novel quinoline-substituted 5H-chromeno [2,3-b] pyridine derivatives as antibacterial agents.

A convenient, straightforward, and effective one-step reaction for the synthesis of a three-component compound of biologically relevant novel 2,4-diamino-5-(8-hydroxyquinolin-7-yl)-5H-chromeno[2,3-b] pyridine-3-carbonitrile derivatives was designed and synthesized. The synthesis was developed by the reaction between salicylaldehyde 1, 8-hydroxyquinoline 2, 2-aminopropene-1,1,3-tricarbonitrile 3, and the catalytic amount of triethylamine in ethanol at 78°C. This methodology has many beneficial features, including the use of inexpensive and non-hazardous starting materials, single-flask reactions, optimized reaction conditions, the termination of intermediate isolation, easy workup, reducing organic waste products, being chromatography-free, and decreasing the reaction time along with quantitative yields with high functional group tolerance. A proposed mechanism with supporting experimental data is presented, including 1H NMR, 13C NMR, 2D NMR (HMBC, COSY, HSQC), mass, and IR spectroscopy, which are used to characterize the complete derivatives. All synthesized compounds were evaluated in vitro for their antibacterial activities against Bacillussubtilis, Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa bacterial strains via the agar-well diffusion method compared with the reference drug gentamicin. The data indicated that compounds 4A, 4F, 4G, 4J, and 4K consistently demonstrated strong antimicrobial activity against Gram-positive and Gram-negative bacteria. Furthermore, a molecular docking investigation was carried out to gain insight into the binding mode of the most promising compounds via the crystal structure of the S. aureus DNA gyrase complex with ciprofloxacin (PDB ID: 2XCT). Density functional theory (DFT) calculations were performed to determine the various molecular properties of the synthesized novel 2,4-diamino-5-(8-hydroxyquinolin-7-yl)-5H-chromeno [2,3-b] pyridine-3-carbonitrile derivatives (4A-4M). On the basis of the reactive sites explored by the molecular electrostatic potential maps, the antibacterial activities of the compounds were screened.

Synthesis and evaluation of the anti-TB activity of novel 7-(2-(4-substituted-phenyl)-4,5-diphenyl-1H-imidazol-1-yl)-4-methyl-2H-chromen-2-one derivatives and their DFT studies for NLO application

A series of novel 7-(2-(4-substituted-phenyl)-4,5-diphenyl-1H-imidazol-1-yl)-4-methyl-2H-chromen-2-one derivatives 5(a-g) have been synthesized and reported as anti-TB activity and non-linear optical applications. The activity results show that compounds 5b, 5c, 5d, 5f, and 5g exhibited excellent efficacy with a MIC value of 3.12 μg/mL, one-fold greater than the reference standard streptomycin (6.26 μg/mL). An in silico molecular docking study was performed against InhA protein and the results were consistent with the experimental results. Computational studies were performed using the DFT method and results reveal that the presence of greater electronegativity atoms increases the HOMO-LUMO energy gap. The NLO properties show that the presence of stronger electron-donating substituents increases the ICT, charge delocalization and β0 values. The NBO analysis shows significant interactions between LP (Lone pair), π* and σ* in compounds account for the high polarization and enhanced NLO activity.

Novel N-Substituted Isatin-Oxoindolin-1H-Benzo[D] Imidazole Fumarate as a New Class of JNK3 Inhibitor: Design, Synthesis, Molecular Modeling and its Biological Activity

Background: A direct synthesis of functionalized dimethyl fumarate derivatives of 2-(2-((E)-(2-oxoindolin-3-ylidene)methyl)-1H-benzo[d]imidazol-1-yl) is achieved via one-pot reac-tion involving 2-methyl-1H-benzo[d]imidazole and appropriate isatin in the presence of DMAD. Methods: Conversely, this one-pot reaction furnished, upon conduction at 60 o C, the 2-(2-((E)-(2-oxoindolin-3-ylidene)methyl)-1H-benzo[d]imidazol-1-yl) products. The biological activities were evaluated against JNK3 kinase. We chose to dock the compounds into the JNK3 binding site in order to comprehend the molecular underpinnings of the observed bioactivities. Results: The structures of the synthesized compound adduct were evidenced from NMR and MS spectral data and further confirmed by single-crystal X-ray diffraction. The biological activities revealing that the introduction of an alkyl group at the 1-position of the isatin moiety produced JNK3 inhibitors with IC50 values in the low micromolar range. Conclusion: This study synthesized a unique compound using a three-component method. Com-pound 4d showed high antitumor activity (IC50 = 6.5 μM) against JNK3 inhibitors, while com-pounds 4c, 4d, and 4f exhibited high selectivity. The research highlights the effectiveness of the one-pot reaction in creating medically useful hybrid compounds, marking a significant advance in medicinal chemistry.

Pyrazole-based N-phenyl pyrazolines: Synthesis, docking, and pharmacological evaluation

A series of methoxy substituted pyrazole based pyrazoline derivatives (4a-j) were synthesized in good to excellent yield from corresponding pyrazole-chalcones (3a-j). All synthesized derivatives were characterized and screened for their in vitro anti-inflammatory, antioxidant, antidiabetic, and antibacterial activities. Among the series, compounds 4f, 4j, 4a, and 4i showed better anti-inflammatory activity as compared to diclofenac sodium. In DPPH free radical scavenging assay, all the compounds were shown excellent activity and moderate to good activity in SO and NO free radical scavenging assay as compared to standard ascorbic acid. Antibacterial screening of synthesized pyrazolines showed that compounds 4f and 4j have significant antibacterial activity. The compounds 4j, 4f, 4h, 4a, and 4c have shown comparable inhibition of alpha-amylase enzyme leading to good antidiabetic activity as compared to standard acarbose. Molecular docking studies suggest that these compounds have strong binding with COX-2 and alpha-amylase enzyme due to significant capability of aromatic and hydrophobic interaction. The outstanding results of reported compounds in all biological screening will pave the way for the design of new drug candidate bearing pyrazole moiety.

Privileged Scaffold Hybridization in the Design of Carbonic Anhydrase Inhibitors.

Human Carbonic Anhydrases (hCA) are enzymes that contribute to cancer's development and progression. Isoforms IX and XII have been identified as potential anticancer targets, and, more specifically, hCA IX is overexpressed in hypoxic tumor cells, where it plays an important role in reprogramming the metabolism. With the aim to find new inhibitors towards IX and XII isoforms, the hybridization of the privileged scaffolds isatin, dihydrothiazole, and benzenesulfonamide was investigated in order to explore how it may affect the activity and selectivity of the hCA isoforms. In this respect, a series of isatin thiazolidinone hybrids have been designed and synthesized and their biological activity and selectivity on hCA I, hCA II, hCA IX, and hCA XII explored. The new compounds exhibited promising inhibitory activity results on isoforms IX and XII in the nanomolar range, which has highlighted the importance of substituents in the isatin ring and in position 3 and 5 of thiazolidinone. In particular, compound 5g was the most active toward hCA IX, while 5f was the most potent inhibitor of hCA XII within the series. When both potency and selectivity were considered, compound 5f appeared as one of the most promising. Additionally, our investigations were supported by molecular docking experiments, which have highlighted the putative binding poses of the most promising compound.

Organocatalytic[3 + 2]Cycloaddition: Synthesis of Quinazoline Containing Sulfonyl 1,2,3‐Triazoles as Potent EGFR Targeting Anti‐Breast Cancer Agents

ABSTRACTA general strategy was developed for the synthesis of new fully decorated 1,2,3‐triazoles (4a–4m and 5a–5g) containing quinazolines from 1‐(4‐nitrophenyl)‐2‐(quinazolin‐8‐ylsulfonyl) ethan‐1‐one and several azides using Ramachary organocatalytic azide‐ketone cycloaddition method. This reaction is reported for the synthesis of fully substituted sulfonyl‐1,2,3‐triazolyl quinazolins at a temperature of 100°C and the yields of the products produced are satisfactory to excellent. In vitro anticancer activity of all these derivatives demonstrated that six compounds, 4d, 4f, 4i, 4j, 5d, and 5e, were effective against two human breast cancer cell lines, MCF‐7 and MDA‐MB‐231. Compounds 4f, 4j, and 5d had more action against both cell lines than Erlotinib. Later, the findings of inhibitory assays of potent compounds 4d, 4f, 4i, 4j, 5d, and 5e against the tyrosine kinase EGFR revealed that compound 5d proved more potent than the reference erlotinib, while 4f and 4j had comparable efficacy. In silico molecular docking studies were also performed on six strong medicines to identify interactions with the EGFR receptor, and the energy estimations were shown to be comparable with the observed IC50 values. Ultimately, using SWISS/ADME and pkCSM, the in silico pharmacokinetic profile of potent compounds 4d, 4f, 4i, 4j, 5d, and 5e was predicted. All of the compounds precisely followed the principles established by Lipinski, Veber, Egan, and Muegge.

Design and synthesis of spiro[pyrrolidine-3,3′-quinoline]-2,2′-dione derivatives as novel antifungal agents targeting chitin synthase

A novel spiro [pyrrolidine-3′,3′-quinoline]-2,2′-dione scaffold was constructed using fragments of quinoline and pyrrolidine. Subsequently, two series of derivatives were designed based on this scaffold. The enzyme inhibition experiments revealed that all designed compounds had moderate to good inhibitory activity against chitin synthase (CHS). The inhibitory effects of compounds 5i, 5j, 8i and 8n were approximately equal to that of control drug polyoxin B (PB, IP = 86.4 ± 2.9 %, IC50 = 0.082 ± 0.013 mM) which is a well-established CHS inhibitor. The results from enzyme kinetic parameters assays proved that these compounds act as non-competitive inhibitors of CHS. The sorbitol protection experiments demonstrated the tested compounds disrupted the synthesis of cell wall, which further verified that the target of these compounds is CHS. The experiments of antimicrobial showed that compounds 5b, 5f, 5i, 5j, 8f, 8i, 8m, 8n and 8o had strong antifungal activity against the four tested pathogenic fungi strains frequently emerging in clinical setting, with MIC values ranging from 4 to 32 μg/mL, which were either superior to or comparable with those of PB or fluconazole. Furthermore, these compounds displayed synergistic or additive effects when combined with fluconazole and these active compounds also showed promising activity against fluconazole-resistant and micafungin-resistant fungi variants. The result of antimicrobial experiments indicated that these compounds had minimal activity to tested bacterial strains. This suggests that they had selective antifungal activity. The results of ADME prediction, in conjunction with the cytotoxicity assay results, indicated that these compounds had favorable pharmacokinetic profiles and low toxicity. In addition, molecular docking studies illustrated that the compound had a strong affinity with the CHS, which was consistent with the results of enzymatic assays. These findings indicated that the designed compounds are non-competitive inhibitors of CHS with good selectivity and broad-spectrum antifungal activity, and possess significant antifungal activity against drug-resistant fungi, suggesting their potential as lead compounds for the development of novel drugs against drug-resistant fungi.

Design, Synthesis and In-Vitro Antimicrobial and Cytotoxic Activity Screening of 5-Carboxamide Substituted 3, 4-Dihydropyrimidine-2 (1H) Ones

This paper describes the synthesis and in vitro biological evaluation of new compounds designated as 5(a-h) and 8(a-f). These compounds were synthesized by the reaction of thiazole derivative (3) or thiadiazole derivative (7) with urea and various aromatic aldehydes 4(a-h) in ethanol. The structures of the synthesized compounds were checked by IR,1H,13C NMR, and Mass spectroscopy. The antibacterial and antifungal activities of the compounds were evaluated against Escherichia coli (Gram-negative), Staphylococcus aureus (Gram-positive), and Candida albicans (fungus) using agar well diffusion, minimum inhibitory concentration (MIC), and minimum bactericidal/fungicidal concentration methods. The cytotoxic activities of these compounds against HT-29 and A-549 cancer cell lines were assessed in vitro by the MTT method. Our studies showed compounds 8c and 8f to have the most expressed antibacterial activity against S. aureus, while compounds 8c and 8d were the most potent against E. coli. Compounds 5h and 8e showed the highest antifungal activity against C. albicans, and compound 5f showed the most potent activity against the tested cancer cell lines.

Discovery of Structural Diversity Guided N‐S Heterocyclic Derivatives Based on Natural Benzothiazole Alkaloids as Potential Cytotoxic Agents

ABSTRACTBenzothiazole alkaloids are a class of rare heterocyclic alkaloids with unique structures and exhibit a wide range of biological activities. So, the aim of this work is to investigate structural diversity‐guided N‐S heterocyclic derivatives based on natural benzothiazole alkaloids as potential cytotoxic agents. Three series of novel benzothiazole derivatives, including 22 compounds, were designed and synthesized using pharmacophore hybridization, and their in vitro cytotoxic activities against Huh‐7 and A875 were fully evaluated. The results indicated that some of these benzothiazole derivatives had significantly good cytotoxic activities against two tested cell lines compared with the positive control 5‐fluorouracil, and other compounds 3f–3i displayed good selectivity between A875 and Huh‐7 cell lines, which might be used as promising lead molecule for discovery of novel benzothiazole‐type cytotoxic agents.

Inhibitory activity and mechanism of thiosemicarbazide derivatives on tyrosinase and their anti-browning activity in fresh apple juice

Exploring tyrosinase inhibitors has been an effective way to find promising anti-browning agents in the food industry. Therefore, a class of thiosemicarbazide derivatives (4a-4m) were synthesized and we investigated the inhibitory mechanism on tyrosinase by fluorescence quenching, copper ion chelating and UV spectra study etc. 2-(2-Chlorobenzyl) hydrazine-1-carbothioamide (4f) (IC50 = 1.21 ± 0.02 μM) is the most active compound of all derivatives, which was defined as a mix-type inhibitor. Additionally, molecular docking and copper ions chelating studies indicated that compound 4f has the ability to inhibit the tyrosinase activity by chelating the copper ions in the active region. Furthermore, compound 4f also exhibited lower cytotoxicity, excellent aqueous solubility and outstanding anti-browning capacity in fresh apple juice. These findings indicated these derivatives could provide more possibility for developing more safer and effective anti-browning agents.

A novel class of potent antiangiogenic and antioxidant pyrazoles: synthesis, bioactivity, docking and ADMET studies.

Aim: Angiogenesis is the hallmark of cancer progression driven by VEGF/VEGFR-2 signalling pathway, inhibition of which could be a solution to tackle the progression of tumour cells and thus arresting their growth.Materials & methods: A novel class of pyrazoles was synthesized using arginine and dibromo ketones. Antiangiogenic activity was performed by in vivo yolk sac method. Antioxidant activity was evaluated by hydroxyl and superoxide radical scavenging assays. Docking studies were performed to determine the pyrazoles' binding potential with VEGFR-2 receptor and VEGF tyrosine kinase. ADMET properties were calculated using SwissADME and admetSAR for drug-likeness.Results: Compounds 5a-e showed significant antiangiogenic effects. Compound 5f exhibited effective hydroxyl and superoxide radical scavenging activities. Docking results confirmed the potential binding efficiency with VEGFR-2 receptor over VEGF tyrosine kinase, thus, functioning as competitive-inhibitors. ADMET studies revealed that the compounds possess favourable drug-like qualities.Conclusion: This study presents a novel class of pyrazoles as promising antioxidant and antiangiogenic agents with favourable drug-likeness properties.

Synthesis of quinoline fused 1,2,3-triazole derivatives via continuous CuAAC and C[sbnd]H arylation; anti-breast cancer, anti-EGFR and HER2 activities, computational studies

Some new quinoline linked fused 1,2,3-triazole hybrids (5a-5o) were synthesized via Cu(I) catalyzed azide-alkyne cycloaddition followed by intramolecular CH arylation in one pot. Further, these derivatives were screened for their anti-breast cancer activity against MCF-7, MDA-MB-468 and MDA-MB-231 cell lines and results were compared with the 5-fluorouracil (5-FU). Out of all, compounds 5a, 5c, 5f, 5g and 5j displayed higher activity than the 5-FU against three cancer cell lines. Compound 5a was more effective in inhibiting both tyrosine kinase EGFR and HER2 enzymes than the Erlotinib and Lapatinib. Furthermore, compound 5j demonstrated greater potency than the Erlotinib against EGFR. Molecular docking studies revealed the important binding features of most potent compounds 5a, 5c, 5f, 5g and 5j with EGFR (PDB ID-4HJO) and HER2 (PDB ID-3RCD) and results were found to be supportive with corresponding IC50 data. Finally, in silico pharmacokinetic studies revealed that compounds 5a, 5c, 5f, 5g and 5j followed Ghose, Egan, Muegge, Lipinski and Veber rules without any deviation.

Synthesis of furo[2,3-c]carbazoles as potent α-glucosidase and α-amylase inhibitors

The carbazole-3-carbaldehyde 2, produced by N-ethyl carbazole via Vilsmeier-Haack reaction, was subjected to Dakin type oxidation with H2O2 and H2SO4 in methanol to produce the carbazole-3-ol 3. The reaction of 3 with a range of commercially available α-haloketones 4a–f in the presence of Al2O3 as catalyst in xylene led to their regio-selective cyclization to afford the furo[2,3-c]carbazoles 5a–f. Identification of the furo[2,3-c]carbazoles 5a–f were performed through 1H NMR,13C NMR, FT-IR and high resolution mass spectrometry. Single crystal X-ray diffraction analysis was employed to further confirm the structures of the some of the targeted compounds. In vitro antidiabetic activities of the newly synthesized furocarbazoles 5a–e were investigated utilizing α-glucosidase and α-amylase enzymes. The biological evaluation revealed the obvious efficiencies of the targeted molecules toward the α-glucosidase enzyme inhibition with the potent IC50 values compared to the standard acarbose. In the case of α-glucosidase inhibition, the furo[2,3-c]carbazoles chloro substituted 5c and nitro substituted 5f were found to be more potent than acarbose with the values of 215.0 and 162.70 μM, respectively. On the other hand, the compound 5f was found to be only promising candidate for α-amylase enzyme but not as effective as the standard acarbose.

Design and synthesis of novel quinoxaline-piperazine linked isoxazole conjugates: Anti-cancer assessment, tyrosine kinase EGFR inhibitory activity, molecular docking and DFT studies

In this paper, we describe the synthesis of a novel series of quinoxaline-piperazine-isoxazole conjugates. We confirmed the structures of the newly synthesised compounds using 1HNMR, Mass, and 13CNMR spectroscopic techniques. The anti-tumour activity was evaluated on two human cancer cell lines, such as MCF-7 (breast) and A-549 (lung). The anti-cancer evaluation dates show that compounds 7f, 7e, and 7 g have more promising anti-cancer activity than the standard drug Erlotinib. We tested three potent compounds (7f, 7e, and 7 g) against a normal breast cell line in a cell survivability test (MCF-10A). Interestingly, none of them killed the cancer cells significantly (IC50 values greater than 88.91 µM). In addition, in vitro tyrosine kinase EGFR inhibitory activity has shown that compounds 7e and 7f display the highest tyrosine kinase EGFR inhibitory potency with an IC50 value of 1.10 and 0.85 µM, respectively, compared to the reference Erlotinib with an IC50 value of 1.24 µM. Furthermore, molecular docking analyses revealed that compounds (7f, 7e, and 7 g) exhibited a higher number of EGFR binding interactions. In this work 7f, the molecule was characterised by using density functional theory (DFT) with B3LYP/6–311G++ (d, p) basis set. The structural parameters were obtained from geometry optimization. Molecular electrostatic potential (MEP), HOMO-LUMO energy gap, and Mulliken atomic charges were calculated. The potent compounds 7f, 7e, and 7 g were subjected to in silico pharmacokinetic assessment by SWISS, ADME, and pkCSM. The three compounds (7e, 7f, and 7 g) intriguingly matched all four of the above-mentioned conditions exactly, with the exception of compound 7f's Ghose rule.

Synthesis and Antifungal Evaluation of Cinnamic Acid-Geraniol Hybrids as Potential Fungicides.

Cinnamic acid and geraniol are two well-known antifungal natural products and widely applied in food and cosmetics industries. To discover novel natural product-based fungicide candidates with more potent activity and good ecological compatibility for the management of plant diseases, a series of cinnamic acid-geraniol hybrids were prepared by means of molecular hybridization and their chemical structures were well confirmed by spectral analysis. The antifungal activities of the target compounds against three phytopathogenic fungi Fusarium graminearum, Gaeumannomycesgraminis (Sacc.) Arx et Oliver var. tritici (Sacc.) Walker, and Valsa mali were evaluated. Among them, compounds 5e and 5f showed the remarkable antifungal activity against G. graminis with the EC50 values of 82.719 and 91.828 μg/mL, respectively; while compounds 5f and 6b exhibited the obvious antifungal activity against V. mali. It suggested that compound 5f can be further optimized for the design of novel broad-spectrum fungicide molecules as the secondary lead compound. In addition, some interesting structure-antifungal activity relationships were obtained. This work will provide some reference and guidance for the further discovery of novel fungicide candidates based on cinnamic acid and geraniol.

Synthesis, cytotoxicity and 99mTc-MIBI tumor cell uptake evaluation of 2-phenylbenzothiazole tagged triazole derivatives.

Aim: The extensive utilization of 2-phenylbenzothiazole due to their wide array of biological activities, particularly in cancer therapy, has caused great attention to explore more potent derivatives.Materials & methods: We report the synthesis of 2-phenylbenzothiazole tagged 1,2,3-triaozle (8) through Cu(I)-catalyzed cycloaddition of alkyne side chain with aryl-substituted azides.Results: The in vitro experiments, using MTT and 99mTc-MIBI cell uptake methods, demonstrated the remarkable anticancer activity of these compounds against A549, SKOV3 and MCF7 cell lines.Conclusion: Compounds 8b, 8f and 8i possessed high cytotoxic activity as compared with doxorubicin. Compound 8g has a similar inhibitory effect on the proliferation of breast cancer cells as doxorubicin. In silico study indicated that compound 8 would be a good lead for the development of new potent anticancer agents.