Compounds 4g Research Articles

Natural Product-Based Drugs Discovery: Semisynthesis and Biological Evaluation of Ester Derivatives from Pregn-5-ene-3β,17α,20(S)-triol.

There is no doubt that derivation of intermediates from natural product is a very efficient way to develop new environmentally friendly pesticide. We synthesis a succession of compounds esterified with pregn-5-ene-3β,17α,20(S)-triol to evaluate its insecticidal and bacteriostatic activity. Otherwise, their structure-activity relationships (SAR) are also discussed. As a result, compounds 7g, 7h, 7j, 7l and 7o exhibit more obvious insecticidal activity against 3rd Mythimna separata Walker (LC50 = 0.60, 0.68, 0.79, 0.85 and 0.78 mg/mL, respectively) than periplocoside F (PSF). Meanwhile, compounds 7g, 7h and 7i perform well inhibitory activity against Pseudomas syringae pv. actinidiae (Psa) in vitro (minimum inhibitory concentration (MIC) values: 0.10-0.25 mg/mL, minimum bactericidal concentration (MBC) values: 0.15-0.35 mg/mL). And SAR analysis indicates that the replacement and position of fluorine atom on benzoyl are highly vital to biological activity.

Design, Synthesis, and Anti-Bacterial Evaluation of Tetrahydrobenzothiophene Derivatives as Lipopolysaccharide Biogenesis Inhibitors

Background: Bacterial infections caused by multidrug-resistant bacteria have emerged as major threats to human communities worldwide. There is a great need to develop new mechanisms by which anti-bacterial agents can combat bacterial antibiotic resistance. Objective: This study aims to synthesize and characterize a series of novel tetrahydrobenzothiophene derivatives and evaluate their anti-bacterial activities. Method: In this study, we have synthesized 2-benzamido-4,5,6,7-tetrahydrobenzo[b]thiophene-3- carboxylic acid derivatives (3a-3r) and investigated their anti-bacterial activities against E. coli, P. aeruginosa, Salmonella, and S. aureus. Results: The MIC values demonstrated that all synthesized derivatives possessed potent anti-bacterial activity properties. Compounds 3b, 3e, 3f, 3g, 3h, 3n, and 3q exhibited in vitro excellent anti-bacterial efficiency. Compounds 3b, 3e, 3f, and 3p were evaluated by in vitro time-kill assay; they displayed concentration- dependent bacteriostatic effects. Compounds 3b, 3e, 3f, and 3p showed moderate water solubility, high stability in plasma, and moderate acute oral toxicity. Conclusion: Most of the 2-benzamido-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylic acid derivatives exhibited potent anti-bacterial activities. The data reported in this paper may guide the design of tetrahydrobenzothiophene derivatives.

Synthesis, Biological Evaluation, and Molecular Modeling Studies of New 1,3,4-Thiadiazole Derivatives as Potent Antimicrobial Agents.

In this work, the synthesis, characterization, and biological activities of a new series of 1,3,4-thiadiazole derivatives were investigated. The structures of final compounds were identified using 1 H-NMR, 13 C-NMR, elemental analysis, and HRMS. All the new synthesized compounds were then screened for their antimicrobial activity against four types of pathogenic bacteria and one fungal strain, by application of the MIC assays, using Ampicilin, Gentamycin, Vancomycin, and Fluconazole as standards. Among the compounds, the MIC values of 4 and 8 μg/mL of the compounds 3f and 3g, respectively, are remarkable and indicate that these compounds are good candidates for antifungal activity. The docking experiments were used to identify the binding forms of produced ligands with sterol 14-demethylase to acquire insight into relevant proteins. The MD performed about 100 ns simulations to validate selected compounds' theoretical studies. Finally, using density functional theory (DFT) to predict reactivity, the chemical characteristics and quantum factors of synthesized compounds were computed. These results were then correlated with the experimental data. Furthermore, computational estimation was performed to predict the ADME properties of the most active compound 3f.

Synthesis of benzylidene-indandione derivatives as quantification of amyloid fibrils

The formation of amyloid fibrils due to its association with fatal diseases, including Alzheimer's, has been investigated by many researchers. These common diseases, mostly become verified when it is too late to be treated. Currently, no cure is available for neurodegenerative diseases, and the process of diagnosing amyloid fibrils in the early stages, while there are fewer amyloid fibrils, has become an issue of interest. To do so, determining new probes with the highest binding affinity to the lowest number of amyloid fibrils is necessary. In this study, we proposed to employ new synthesized benzylidene-indandione derivatives as amyloid fibrils fluorescent detection probes. Native soluble proteins of insulin, bovine serum albumin (BSA), BSA amorphous aggregation, and insulin amyloid fibrils were used to evaluate our compounds' specificity to the amyloid structure. While ten synthesized compounds were examined individually, four of them including 3d, 3g, 3i, and 3j showed a high binding affinity with selectivity and specificity to amyloid fibrils, and their binding properties were also confirmed with in silico analysis. The drug-likeness prediction results for selected compounds by Swiss ADME server shows a satisfactory percentage of blood-brain barrier (BBB) permeability and gastrointestinal (GI) absorption for the compounds 3g, 3i, and 3j. More evaluation is needed to determine all properties of compounds in vitro and in vivo.

Ultrasound-Assisted Synthesis of Piperidinyl-Quinoline Acylhydrazones as New Anti-Alzheimer's Agents: Assessment of Cholinesterase Inhibitory Profile, Molecular Docking Analysis, and Drug-like Properties.

Alzheimer's disease (AD) is one of the progressive neurological disorders and the main cause of dementia all over the world. The multifactorial nature of Alzheimer's disease is a reason for the lack of effective drugs as well as a basis for the development of new structural leads. In addition, the appalling side effects such as nausea, vomiting, loss of appetite, muscle cramps, and headaches associated with the marketed treatment modalities and many failed clinical trials significantly limit the use of drugs and alarm for a detailed understanding of disease heterogeneity and the development of preventive and multifaceted remedial approach desperately. With this motivation, we herein report a diverse series of piperidinyl-quinoline acylhydrazone therapeutics as selective as well as potent inhibitors of cholinesterase enzymes. Ultrasound-assisted conjugation of 6/8-methyl-2-(piperidin-1-yl)quinoline-3-carbaldehydes (4a,b) and (un)substituted aromatic acid hydrazides (7a-m) provided facile access to target compounds (8a-m and 9a-j) in 4-6 min in excellent yields. The structures were fully established using spectroscopic techniques such as FTIR, 1H- and 13C NMR, and purity was estimated using elemental analysis. The synthesized compounds were investigated for their cholinesterase inhibitory potential. In vitro enzymatic studies revealed potent and selective inhibitors of AChE and BuChE. Compound 8c showed remarkable results and emerged as a lead candidate for the inhibition of AChE with an IC50 value of 5.3 ± 0.51 µM. The inhibitory strength of the optimal compound was 3-fold higher compared to neostigmine (IC50 = 16.3 ± 1.12 µM). Compound 8g exhibited the highest potency and inhibited the BuChE selectively with an IC50 value of 1.31 ± 0.05 µM. Several compounds, such as 8a-c, also displayed dual inhibitory strength, and acquired data were superior to the standard drugs. In vitro results were further supported by molecular docking analysis, where potent compounds revealed various important interactions with the key amino acid residues in the active site of both enzymes. Molecular dynamics simulation data, as well as physicochemical properties of the lead compounds, supported the identified class of hybrid compounds as a promising avenue for the discovery and development of new molecules for multifactorial diseases, such as Alzheimer's disease (AD).

Synthesis and Biological Screening of New 2-(5-Aryl-1-phenyl-1H-pyrazol-3-yl)-4-aryl Thiazole Derivatives as Potential Antimicrobial Agents.

A new series of 2-(5-aryl-1-phenyl-1H-pyrazol-3-yl)-4-aryl thiazoles (10a-ab) have been synthesized by a cyclocondensation reaction of 5-aryl-1-phenyl-1H-pyrazole-3-carbothioamide (7a-d) with substituted phenacyl bromide (8a-f). The structure of newly synthesized 2-(5-aryl-1-phenyl-1H-pyrazol-3-yl)-4-aryl thiazole (10a-ab) derivatives was characterized by spectroscopic analysis. The compounds 10a-ab were evaluated for in vitro antibacterial activity against Escherichia coli (NCIM 2574), Proteus mirabilis (NCIM 2388), Bacillus subtilis (NCIM 2063), Staphylococcus aureus (NCIM 2178), and in vitro antifungal activity against Aspergillus niger (ATCC 504) and Candida albicans (NCIM 3100). Among the twenty-eight pyrazolyl-thiazole derivatives, six compounds, 10g, 10h, 10i, 10j, 10o, and 10t, showed good activity against P. mirabilis; four compounds 10q, 10u, 10y, and 10z showed good activity against S. aureus; and twenty-four derivatives showed good antifungal activity against A. niger. Compounds 10g, 10q, 10r, 10s, and 10ab showed comparable activity with respect to the reference drug Ravuconazole. Thus, the significant antimicrobial activity of 2-(5-aryl-1-phenyl-1H-pyrazol-3-yl)-4-aryl thiazole (10a-ab) derivatives prompted that these scaffolds could assist in the development of lead compounds to treat microbial infections.

Design, Synthesis, and Pharmacology of New Triazole-Containing Quinolinones as CNS Active Agents.

Epilepsy and major depressive disorder are the two of the most common central nervous system (CNS) diseases. Clinicians and patients call for new antidepressants, antiseizure medicines, and in particular drugs for depression and epilepsy comorbidities. In this work, a dozen new triazole-quinolinones were designed, synthesized, and investigated as CNS active agents. All compounds reduced the immobility time significantly during the forced swim test (FST) in mice at the dosage of 50 mg/kg. Compounds 3f-3j gave superior performance over fluoxetine in the FST with more reductions of the immobility time. Compound 3g also reduced immobility time significantly in a tail suspension test (TST) at the dosage of 50 mg/kg, though its anti-immobility activity was inferior to that of fluoxetine. An open field test was carried out and it eliminated the false-positive possibility of 3g in the FST and TST, which complementarily supported the antidepressant activity of 3g. We also found that almost all compounds except 3k exhibited antiseizure activity in the maximal electroshock seizure (MES) model at 100 or 300 mg/kg. Compounds 3c, 3f, and 3g displayed the ED50 of 63.4, 78.9, and 84.9 mg/kg, and TD50 of 264.1, 253.5, and 439.9 mg/kg, respectively. ELISA assays proved that the mechanism for the antiseizure and antidepressant activities of compound 3g was via affecting the concentration of GABA in mice brain. The molecular docking study showed a good interaction between 3g and the amino acid residue of the GABAA receptor. Excellent drug-like properties and pharmacokinetic properties of compound 3a-l were also predicted by Discovery Studio. These findings provided a new skeleton to develop agents for the treatment of epilepsy and depression comorbidities.

Synthesis, computational study, solvatochromism and biological studies of thiazole-owing hydrazone derivatives

In the present work, we have synthesized thiazole-hydrazone conjugates 5(a–h) and characterized them using various analytical techniques such as UV, IR, NMR, and mass spectrometry. Solvatochromic properties were evaluated in ten solvents with different polarity and quantum chemical parameters using a DFT study. The antibacterial activity results revealed that compounds 5c, 5d and 5g exhibited good efficacy and that the remaining compounds displayed significant activity. The synthesized compounds were screened for their cytotoxic activity against HepG2 and MCF-7 cell lines, and all the synthesized compounds exhibited significant potency towards the screened cancer cell lines. The anti-inflammatory efficacy of the synthesized thiazole derivatives was determined against MMP-2 and MMP-9, and some of the compounds showed significant activity. Furthermore, the in silico molecular docking was performed with the COX-2 receptor.

Synthesis, antioxidant activity, docking simulation, and computational investigation of novel heterocyclic compounds and Schiff bases from picric acid

In this elucidation, we used the available picric acid commercial for the synthesis of different heterocyclics such as carbothioamide and 1,3,4-oxadiazole and different Schiff bases derivatives. Furthermore, the synthesis route of 1,3,4-oxadiazole derivatives is known in literature but we used here an aprotic solvent without basic conditions. Moreover, all the synthesized compounds exhibited antioxidant capacity, total phenolic content (TPC), total flavonoid substance amount (TF), iron (III) reducing antioxidant power (FRAP), and DPPH radical scavenging activity. The compounds 5d, 5e, and 5f showed excellent activity in all of the TPC, TF, FRAP, and DPPH parameters compared to the standards used. In addition, it was determined from the statistical studies that compound 4a and 5b as TPC and TF content; compounds 5c, 5e, and 5f as TPC content, and compounds 5a, 5c, and 5g as TF content showed similar, good-moderate effectiveness compared to the standards used. Also the docking stimulation of synthesized compounds with different proteins PDBID:2CDU and PDBID: 3RP8 showed excellent binding energy with Schiff base compounds, in addition to the optimization of these heterocycles with DFT/B3LYP/6-31 basis and determination there physical descriptor's which indicated the activity of Schiff base with correlated with biological evaluation.

A New Concept of Enhancing the Anticancer Activity of Manganese Terpyridine Complex by Oxygen-Containing Substituent Modification.

Eleven manganese 4'-substituted-2,2':6',2″-terpyridine complexes (1a-1c and 2a-2h) with three non-oxygen-containing substituents (L1a-L1c: phenyl, naphthalen-2-yl and naphthalen-1-yl, L1a-L1c) and eight oxygen-containing substituents (L2a-L2h: 4-hydroxyl-phenyl, 3-hydroxyl-phenyl, 2-hydroxyl-phenyl, 4-methoxyl-phenyl, 4-carboxyl-phenyl, 4-(methylsulfonyl)phenyl, 4-nitrophenyl and furan-2-yl) were prepared and characterized by IR, elemental analysis or single crystal X-ray diffraction. In vitro data demonstrate that all of these show higher antiproliferative activities than cisplatin against five human carcinoma cell lines: A549, Bel-7402, Eca-109, HeLa and MCF-7. Compound 2d presents the strongest antiproliferative effect against A549 and HeLa cells, with IC50 values being 0.281 μM and 0.356 μM, respectively. The lowest IC50 values against Bel-7402 (0.523 μM) Eca-109 (0.514 μM) and MCF-7 (0.356 μM) were obtained for compounds 2h, 2g and 2c, respectively. Compound 2g with a nitro group showed the best results on the whole, with relevantly low IC50 values against all the tested tumor cells. The DNA interactions with these compounds were studied by circular dichroism spectroscopic and molecular modeling methods. Spectrophotometric results revealed that the compounds have strong affinities in binding with DNA as intercalators, and the binding induces DNA conformational transition. Molecular docking studies indicate that the binding is contributed by the π-π stacking and hydrogen bonds. The anticancer activities of the compounds are correlated with their DNA binding ability, and the modification of oxygen-containing substituents significantly enhanced the anticancer activity, which could provide a new rationale for the future design of terpyridine-based metal complexes with antitumor potential.

Thioquinoline derivatives conjugated to thiosemicarbazide as potent tyrosinase inhibitors with anti-melanogenesis properties

In the present study, a series of aryl-substituted thioqunoline conjugated to thiosemicarbazide were rationally designed and synthesized. The formation of target compounds was confirmed by spectral characterization techniques such as IR, 1H-NMR, 13C-NMR, ESI–MS, and elemental analysis. Among the synthesized derivatives, compound 10g bearing para-chlorophenyl moiety was proved to be the most potent tyrosinase inhibitor with an IC50 value of 25.75 ± 0.19 µM. Compound 10g as the most potent derivative exhibited a noncompetitive inhibition pattern against tyrosinase in the kinetic study. Furthermore, the in silico cavity detection, as well as the molecular docking assessments, were performed to follow the behavior of 10g within the proposed binding site. Besides, the toxicity of 10g and its potency to reduce the melanin content on A375 cell lines were also measured. Consequently, aryl-substituted thioqunolines conjugated to thiosemicarbazide might be a promising candidate in the cosmetics, medicine, and food industry as tyrosinase inhibitors.

Synthesis and discovery of potential tyrosinase inhibitor of new coumarin-based thiophenyl-pyrazolylthiazole nuclei: In vitro evaluation, cytotoxicity, kinetic, and computational studies.

A well-known key enzyme in melanogenesis and hyperpigmentation is tyrosinase. The present study introduces a novel series of thiophenyl-pyrazolylthiazole-coumarin hybrids (6a-6h) as tyrosinase inhibitors. The in-vitro tyrosinase inhibition results indicated that all compounds have strong tyrosinase inhibitory activity, particularly compound 6g (IC50 = 0.043 ± 0.006 μM), was identified as the most active compound compared to the positive control (kojic acid, IC50 = 18.521 ± 1.162 μM). Lineweaver-Burk plots were employed to analyze the kinetic mechanism, and compound 6g formed an enzyme-inhibitor complex by inhibiting tyrosinase non-competitively. Furthermore, all compounds demonstrated excellent antioxidant activity against DPPH. MTT assay was used to screen the cytotoxicity of all compounds on B16F10 melanoma cells, and they had no toxic effect on the cells. The binding affinity of compounds with tyrosinase was also investigated using molecular docking, and the ligands displayed good binding energy values. These molecules could be a promising lead for skin pigmentation and associated diseases as nontoxic pharmacological scaffolds.

New benzimidazole-oxadiazole derivatives: Synthesis, α-glucosidase, α-amylase activity, and molecular modeling studies as potential antidiabetic agents.

Benzimidazole-1,3,4-oxadiazole derivatives (5a-z) were synthesized and characterized with different spectroscopic techniques such as 1 H NMR, 13 C NMR, and HRMS. The synthesized analogs were examined against α-glucosidase and α-amylase enzymes to determine their antidiabetic potential. Compounds 5g and 5q showed the most activity with 35.04 ± 1.28 and 47.60 ± 2.16 µg/mL when compared with the reference drug acarbose (IC50 = 54.63 ± 1.95 µg/mL). Compounds 5g, 5o, 5s, and 5x were screened against the α-amylase enzyme and were found to show excellent potential, with IC50 values ranging from 22.39 ± 1.40 to 32.07 ± 1.55 µg/mL, when compared with the standard acarbose (IC50 = 46.21 ± 1.49 µg/mL). The antioxidant activities of the effective compounds (5o, 5g, 5s, 5x, and 5q) were evaluated by TAS methods. A molecular docking research study was conducted to identify the active site and explain the functions of the active chemicals. To investigate the most likely binding mode of the substances 5g, 5o, 5q, 5s, and 5x, a molecular dynamics simulation was also carried out.

Design and synthesis of some novel hybrid molecules based on 4-thiazolidinone bearing pyridine-pyrazole scaffolds: molecular docking and molecular dynamics simulations of its major constituent onto DNA gyrase inhibition.

Due to multidrug resistance, microbial infections have become significant on a global level. As infections caused by several resistant bacteria and fungi severely harm mankind, scientists have developed new antibiotics to combat these infections. In order to develop novel antimicrobial agents, a series of 4-thiazolidinone-based 5-arylidene hybrids (5a-o) have been designed and synthesized to evaluate their antibacterial and antifungal activities. For the determination of the structure of a novel synthesized hybrid, various spectral techniques, e.g., IR, 1H NMR, 13C NMR, and Mass spectroscopy, were used. Two bacterial gram-negative (Escherichia coli and Pseudomonas aeruginosa), two gram-positive strains (Staphylococcus aureus and Streptococcus pyogenes), and one fungal strain (Candida albicans) were used to evaluate antimicrobial activity. Compounds 5c, 5g, and 5i were effective due to their MIC values of 62.5μg/mL against tested bacterial strains (S. pyogenes (5c), P. aeruginosa (5g), and E. coli (5i), respectively.) and 250μg/mL against C. albicans fungal strains, respectively. Additionally, molecular docking and 100ns molecular dynamic simulations were carried out to investigate the stability of molecular contacts and to establish how the newly synthesized inhibitors fit together in the most stable conformations.

2-Phenylpyridine Derivatives: Synthesis and Insecticidal Activity against Mythimna separata, Aphis craccivora, and Tetranychus cinnabarinus

The increase in the insecticide resistance of pests, such as Mythimna separata, Aphis craccivora Koch, and Tetranychus cinnabarinus, necessitates the development of new heterocyclic compounds with high insecticidal activity. A series of novel 2-phenylpyridine derivatives containing N-phenylbenzamide moieties were designed and synthesised with Suzuki-Miyaura cross-coupling, nucleophilic substitution, and amidation reactions. The reaction conditions in each step are mild, and the product is easy to separate (yield is about 85%). The structures of the compounds were characterised using 1H and 13C NMR spectroscopy and HRMS. Moreover, the insecticidal activity of the compounds was analysed using the leaf dipping method. The compounds 5a, 5d, 5g, 5h, and 5k at 500 mg/L exhibited 100% inhibition against Mythimna separata. Therefore, the 2-phenylpyridine moieties have the potential to lead to the discovery of novel and effective insecticides.

Exploring novel fluorine-rich fuberidazole derivatives as hypoxic cancer inhibitors: Design, synthesis, pharmacokinetics, molecular docking, and DFT evaluations.

Sixteen fuberidazole derivatives as potential new anticancer bioreductive prodrugs were prepared and characterized. The in vitro anticancer potential was examined to explore their cytotoxic properties by employing apoptosis, DNA damage, and proliferation tests on chosen hypoxic cancer cells. Eight substances (Compound 5a, 5c, 5d, 5e, 5g, 5h, 5i, and 5m) showed promising cytotoxicity values compared to the standard control. The potential of compounds was also examined through in silico studies (against human serum albumin), including chem-informatics, to understand the structure-activity relationship (SAR), pharmacochemical strength, and the mode of interactions responsible for their action. The DFT calculations revealed that only the 5b compound showed the lowest ΔET (2.29 eV) while 5i showed relatively highest βtot (69.89 x 10-31 esu), highest αave (3.18 x 10-23 esu), and dipole moment (6.49 Debye). This study presents a novel class of fuberidazole derivatives with selectivity toward hypoxic cancer cells.

Discovery of New Boswellic Acid Hybrid 1H-1,2,3-Triazoles for Diabetic Management: In Vitro and In Silico Studies.

A series of 24 new 1H-1,2,3-triazole hybrids of 3-O-acetyl-11-keto-β-boswellic acid (β-AKBA (1)) and 11-keto-β-boswellic acid (β-KBA (2)) was designed and synthesized by employing "click" chemistry in a highly efficient manner. The 1,3-dipolar cycloaddition reaction between β-AKBA-propargyl ester intermediate 3 or β-KBA-propargyl ester intermediate 4 with substituted aromatic azides 5a-5k in the presence of copper iodide (CuI) and Hünig's base furnished the desired products-1H-1,2,3-triazole hybrids of β-AKBA (6a-6k) and β-KBA (7a-7k)-in high yields. All new synthesized compounds were characterized by 1H-, 13C-NMR spectroscopy, and HR-ESI-MS spectrometry. Furthermore, their α-glucosidase-inhibitory activity was evaluated in vitro. Interestingly, the results obtained from the α-glucosidase-inhibitory assay revealed that all the synthesized derivatives are highly potent inhibitors, with IC50 values ranging from 0.22 to 5.32 µM. Among all the compounds, 6f, 7h, 6j, 6h, 6g, 6c, 6k, 7g, and 7k exhibited exceptional inhibitory potency and were found to be several times more potent than the parent compounds 1 and 2, as well as standard acarbose. Kinetic studies of compounds 6g and 7h exhibited competitive and mixed types of inhibition, with ki values of 0.84 ± 0.007 and 1.18 ± 0.0012 µM, respectively. Molecular docking was carried out to investigate the binding modes of these compounds with α-glucosidase. The molecular docking interactions indicated that that all compounds are well fitted in the active site of α-glucosidase, where His280, Gln279, Asp215, His351, Arg442, and Arg315 mainly stabilize the binding of these compounds. The current study demonstrates the usefulness of incorporating a 1H-1,2,3-triazole moiety into the medicinally fascinating boswellic acids skeleton.

Design and Metal-Free Synthesis and Cytotoxicity Evaluation of 5Hchromeno[ 4,3-b]pyridine Derivatives as Anti-Proliferative Agents

Background:A novel metal-free approach is reported for the synthesis of 5H-chromeno[4,3-b]pyridine derivatives. Indeed, chromene derivatives are found to exhibit a broad spectrum of biological activities such as antibacterial, antirhinovirus, antioxidant, cytotoxic, anticancer, and antimicrobial properties.Methods:This method provides an easy access to a large number of 5H-chromeno[4,3-b]pyridine scaffolds by the condensation of 3-formylchromene with -enaminoesters under thermal conditions. All compounds are well characterized by NMR, IR and mass spectrometry. This is a safe and convenient protocol.Results:Thus newly synthesized compounds are evaluated for their cytotoxicity against four human cancer cell lines, such as B16 (Skin cancer), DU145 (Prostate cancer), Hela (Cervical cancer) and CHO (Chinese hamster ovary).Conclusion:Among them, compounds 3n and 3o shows an excellent anti-proliferation activity against CHO (IC50 12.33+1.13 μM), Hela (IC50 22.33+0.51 μM), and B16 (IC50 27.61+0.8 μM) cell lines, while compounds 3c, 3g and 3q exhibits promising anti-proliferation against above four human cancer cell lines with IC50 14.96+1.9, 15.59+0.9, 13.8+0.06 μM, respectively, compared with a standard drug Doxorubicin & Mitomycin.

Investigation of Antimicrobial Activity of Some Ethylparaben Hydrazide-Hydrazone Derivatives.

The development of antimicrobial molecules discussed with considerable achievement over the past decades provided many classes of semisynthetic or synthetic compounds. Resistance to many antimicrobial agents requires the discovery of novel molecules. In this study, ten ethylparaben hydrazide-hydrazone derivatives, the previously reported, were evaluated for their in vitro antibacterial and antifungal activities. The microbroth dilution method was used for the determination of the minimum inhibitory concentration (MIC) values of the novel molecules. The antimicrobial activities of the molecules were found in a wide range with MIC values of 2-256 μg/mL. The synthesized compounds showed good to moderate antimicrobial activity compared with the standards. Among the synthesized molecules, compound 3g showed the best antimicrobial activity at 2 μg/mL against Staphylococcus aureus strain (ATCC 29213). Ethylparaben hydrazide-hydrazone compounds in our study were found to have antimicrobial activities. Ethylparaben is currently used as an antibacterial agent and preservative for preparations. These studies are necessary since they detect the relationship between the substitutions and activity.

Novel heterocyclic analogues of bergenin as anti-mitotic agents: Design, synthesis, biological evaluation and molecular docking study

In continuation of our effortsin the development of natural product-based tubulin inhibitors with potential anti-mitotic activities, a novel bergenin hybrids incorporating sulfonate and 1, 2, 3-triazole moieties at carbon-11 were designed and synthesized. The in vitro cytotoxic activity of these derivatives (3a-i, 6a-k and 7a-g) was assessed against various cancer cells and majority of derivatives in this study were shown potent anticancer activity against tested cancer cells than that parent compound. Especially, the compounds 3i, 6g, and 6h exhibited significant activity against HeLa cell line with IC50 of 9.1 ± 0.4, 10 ± 0.2, and 7 ± 0.1 µM, which is comparable to the standard drug, nocodazole (IC50 5.2 ± 1.3 µM). The flowcytometry analysis indicated that the compounds 3i, 6g, and 6h arrest cells at G2/M phase and increased expression of mitotic markers, Cyclin B1 and PLK1 proteins. In addition, 3i, 6g, and 6h generate the oxidative stress and induce apoptosis in the HeLa cells was confirmed with flowcytometry analysis. Molecular docking studies revealed that the compounds 3i, 6g, and 6h have significant binding energy with PLK1 and Cyclin B1 protein and regulating the apoptotic process.