Compounds 3e Research Articles

Halogen substituted aurones as potential apoptotic agents: synthesis, anticancer evaluation, molecular docking, ADMET and DFT study

A series of halogen-substituted aurone derivatives (2a-k) were synthesized and evaluated for an anti-proliferative study against NCI 60 cancer cell line panel and showed that most of the compounds predominantly exhibited promising activity against MCF-7. Compound 2e exhibited promising anticancer activity against the MCF-7 cancer cell line with 84.98% percentage growth inhibition in a single dose assay of 10 μM with an IC50 value of 8.157 ± 0.713 μM. In apoptotic assay, the effect of compound 2e on the cell cycle progression indicated that exposure of MCF-7 cells to compound 2e induced a significant disruption in the cell cycle profile including a time-dependent decrease in the cell population at G0/G1 and G2/M phase and arrests the cell cycle at the S phase. In silico, molecular docking ADME and toxicity studies of all compounds were also carried out. The docking study revealed that all the aurone derivatives displayed good docking scores ranging from −7.066 to −8.573. The results of Molecular Electrostatic Potential Mapping (MESP) and Density Functional Theory (DFT) studies of the most active compound 2e and least active compound 2k also favoured the experimental results.

Synthesis of Novel Quinazolinone Analogues for Quorum Sensing Inhibition.

As bacteria continue to develop resistance mechanisms against antimicrobials, an alternative method to tackle this global concern must be developed. As the pqs system is the most well-known and responsible for biofilm and pyocyanin production, quinazolinone inhibitors of the pqs system in P. aeruginosa were developed. Molecular docking following a rationalised medicinal chemistry approach was adopted to design these analogues. An analysis of docking data suggested that compound 6b could bind with the key residues in the ligand binding domain of PqsR in a similar fashion to the known antagonist M64. The modification of cyclic groups at the 3-position of the quinazolinone core, the introduction of a halogen at the aromatic core and the modification of the terminal group with aromatic and aliphatic chains were investigated to guide the synthesis of a library of 16 quinazolinone analogues. All quinazolinone analogues were tested in vitro for pqs inhibition, with the most active compounds 6b and 6e being tested for biofilm and growth inhibition in P. aeruginosa (PAO1). Compound 6b displayed the highest pqs inhibitory activity (73.4%, 72.1% and 53.7% at 100, 50 and 25 µM, respectively) with no bacterial growth inhibition. However, compounds 6b and 6e only inhibited biofilm formation by 10% and 5%, respectively.

Development of novel 1,2,4-triazole containing compounds with anticancer and potent anti-CB1 activity

There is still an unmet need for novel and improved anti-cancer compounds. Nitrogen atoms have heterocyclic ring moieties, which have been shown to have powerful anticancer properties in both natural and synthetic derivatives. Due to their dipole character, hydrogen bonding capacity, rigidity and solubility, 1,2,4-triazoles are particularly effective pharmacophores, interacting with biological receptors with high affinity. Thus, novel 1,2,4-triazole-containing molecular derivatives were synthesized using green chemistry methods, microwave irradiation and ultrasonication, and these methods’ operational simplicity and maximum greener synthetic efficiency with green chemistry metrics calculations will be attractive for academic and industrial research and tested against three distinct human cancer cell lines including PANC1 (pancreatic cancer), DU145 (prostate cancer), MCF7 (breast cancer) and one fibroblast cell line (HDF). Here, we showed that compounds 5e and 5f were similar to CB1 antagonists in structure, binding affinity and poses. In addition, compounds 5e–g decreased the viability of pancreatic and prostate cancer cells, albeit with cytotoxicity to HDF cells. The IC50 values for PANC1 cells were between 5.9 and 7.3 µM for compounds 5e–g. Cell cycle analysis showed that the effect of compounds 5e–g in cancer cell growth was largely due to cell cycle arrest at S-phase. In sum, novel 1,2,4-triazole-containing compounds with anticancer and potent anti-CB1 activity have been developed. Communicated by Ramaswamy H. Sarma

Design, synthesis, evaluation of biological activities and molecular docking and dynamic studies of novel acetazolamide analog compounds

Modification of drugs used in the clinic is a frequently used method with regards to medicinal chemistry in the development of new drugs. Acetazolamide is a drug in clinical use as a CA inhibitor. Within the scope of this study, the 'N-(5-sulfamoyl-1,3,4-thiadiazol-2-yl) acetamide’ structure, which is acetazolamide residue, was kept constant; various mercaptan substitutions were made from methylene adjacent to the carbonyl group in the structure. Compounds 4c, 4d, 4e, 4 g, 4h, 4i, and 4j exhibited inhibitor activity against CA enzyme with IC50=0.238 ± 0.010, 0.161 ± 0.007, 0.067 ± 0.002, 0.084 ± 0.003, 0.033 ± 0.001, 0.049 ± 0.002 and 0.187 ± 0.008 µM, respectively. The intermolecular interactions of the promising compounds with aromatase enzyme were investigated through the SP docking approach, which revealed significant binding interaction energies associated with these compounds. To measure the stability of the compounds in the enzyme active site, dynamic studies were performed at 100 ns. In addition to the RMSD, RMSF parameters, the interaction ratios of compound 4h with amino acids in the enzyme active site and the interaction histograms were also investigated. The results obtained are quite promising. Continuous interactions were exhibited with Thr199, Glu106, His96, His94 and His119, which are important for the CA enzyme. Communicated by Ramaswamy H. Sarma

Synthesis, characterization, molecular docking, in silico ADME study, and in vitro cytotoxicity evaluation of new pyridine derivatives of nabumetone.

New pyridine derivatives of nabumetone containing 2-amino 3-cyano moieties were synthesized and aimed to introduce new EGFR kinase inhibitors through two methods either by synthesis of chalcone derivatives initially (1a-d)
 followed by reacting it with malononitrile and ammonium acetate to form (2a-d) or from a one-pot synthesis of all reactants together to synthesis compounds (2a-e). Melting point, and FT-IR spectra were used to characterize all the synthesized compounds and were confirmed by 1H-NMR, and 13C-NMR spectroscopy. The final compounds (2a-e) were investigated in vitro against A549 (lung cancer cell line) and WRL68 (human normal cell line). compounds (2a, 2b, and 2e) produced marked cytotoxic activity with IC50 (24.62, 23.43, and 24.06 μg/ml) respectively, higher than what obtained from erlotinib with IC50 (25 μg/ml) as a reference drug. Measuring the selectivity index (SI) reveals that all the compounds have high selectivity especially compound (2a) being the most selective towards cancerous cells rather than normal cells with SI two folds higher than erlotinib. The molecular docking study reveals good binding to the EGFR kinase that has a good correlation to the MTT Assay results. In silico ADME study exposes that this synthesized series not only have interesting activity but also shows promised pharmacokinetic properties.

Synthesis and Evaluation of Novel Metacetamol Derivatives with Hydrazone Moiety as Anticancer and Antimicrobial Agents.

By exploiting the wide biological potential of the hydrazone scaffold, a series of hydrazone derivatives were synthesized, starting from N-(3-hydroxyphenyl)acetamide (metacetamol). The structures of the compounds were determined using IR, 1H and 13C-NMR, and mass spectroscopic methods. The obtained molecules (3a-j) were evaluated for their anticancer potential against MDA-MB-231 and MCF-7 breast cancer cell lines. According to the CCK-8 assay, all tested compounds showed moderate to potent anticancer activity. Among them, N-(3-(2-(2-(4-nitrobenzylidene)hydrazineyl)-2-oxoethoxy)phenyl)acetamide (3e) was found to be the most effective derivative with an IC50 value of 9.89 μM against MDA-MB-231 cell lines. This compound was further tested for its potential effects on the apoptotic pathway. Molecular docking studies was also carried out for 3e in the colchicine binding pocket of tubulin. Additionally, compound 3e also demonstrated effective antifungal activity, particularly against Candida krusei (MIC = 8 mg/ml), indicating that nitro group at the 4th position of the phenyl ring was the most preferable substituent for both cytotoxic and antimicrobial activity. Our preliminary findings suggest that compound 3e could be exploited as a leading structure for further anticancer and antifungal drug development.

Development of novel celastrol-ligustrazine hybrids as potent peroxiredoxin 1 inhibitors against lung cancer

The disruption of oxidation-reduction equilibrium through inhibiting reactive oxygen species (ROS) clearance or enhancing ROS production has emerged as a novel and promising strategy for cancer therapy. Herein, a series of celastrol-ligustrazine hybrids were designed and synthesized as effective ROS promoters, and their biological activities were further evaluated. Among them, compound 7e stood out as the most potent peroxiredoxin 1 (PRDX1) inhibitor (IC50 = 0.164 μM), which was significant super to the recognized PRDX1 inhibitor Conoidin A (IC50 = 14.80 μM) and the control compound celastrol (IC50 = 1.622 μM). Furthermore, 7e dramatically promoted intracellular ROS accumulation, and inhibited the proliferation, invasion and migration of cancer cells besides inducing apoptosis in vitro. Additionally, 7e suppressed the key signaling pathways (AKT and ERK) and promoted the expression of apoptosis-related proteins (cleaved caspase-3/8 and cleaved PARP) in A549 cells, which resulted in the prevention of tumor progression. Most importantly, compound 7e (TGI = 77.47%) showed more considerable in vivo antitumor efficacy and less toxicity than celastrol (TGI = 71.00%). Overall, this work indicates 7e as the most potential PRDX1 inhibitor and may be a promising candidate for the therapy of lung cancer.

New Anthranilic Acid Hydrazones as Fenamate Isosteres: Synthesis, Characterization, Molecular Docking, Dynamics & in silico ADME, in vitro Anti-inflammatory and Anti-cancer Activity Studies.

In this study, twenty new anthranilic acid hydrazones 6-9 (a-e) were synthesizedand their structures were characterized by Fourier-transform Infrared (FTIR), Nuclear Magnetic Resonance (1H NMR - 13C NMR), and High-resolution Mass Spectroscopy (HRMS). The inhibitory effects of thecompounds against COX-II were evaluated. IC50 values of the compounds were found in the range of >200 - 0.32 µM and compounds 6e, 8d, 8e, 9b, 9c, and 9e were determined to be the most effective inhibitors. Cytotoxic effects of the most potent compounds were investigated against human hepatoblastoma (Hep-G2) and human healthy embryonic kidney (Hek-293) cell lines. Doxorubicin (IC50: 8.68 ± 0.16 µM for Hep-G2, 55.29 ± 0.56 µM for Hek-293) was used as standard.8e is the most active compound, with low IC50against Hep-G2 (4.80 ± 0.04 µM), high against Hek-293 (159.30 ± 3.12), and high selectivity (33.15). Finally, molecular docking and dynamics studies were performed to understand ligand-protein interactions between the most potent compounds and COX II, Epidermal Growth Factor Receptor (EGFR), and Transforming Growth Factor beta II (TGF-βII). The docking scores were calculated in the range of -10.609 - -6.705 kcal/mol for COX-II, -8.652 - -7.743 kcal/mol for EGFR and -10.708 - -8.596 kcal/mol for TGF-βII.

Discovery of a novel dual-target inhibitor of CDK12 and PARP1 that induces synthetic lethality for treatment of triple-negative breast cancer

Triple negative breast cancer (TNBC) is one of the most aggressive breast tumors, with a high rate of recurrence and metastasis as well as a poor prognosis. Consequently, it is urgent to find new targeted therapeutic strategies and development of corresponding drugs. Previous studies have shown that CDK12 inhibitors in combination with PARP1 inhibitors is able to induce synthetic lethality in TNBC cells. Here, we reported simultaneously inhibition of CDK12 and PARP1 by genetic or pharmacological approaches synergistically inhibited the proliferation of TNBC cells. Then, a series of small molecule inhibitors targeting both CDK12 and PARP1 were designed and synthesized. The new dual-target inhibitor (12e) showed potent inhibitory activity against CDK12 (IC50 = 285 nM) and PARP1 (IC50 = 34 nM), as well as good anti-proliferative effects in TNBC cell lines. Meanwhile, compound 12e showed favorable synergistic anti-tumor efficacy in cells and xenografts by inhibiting DNA damage repair, promoting cell cycle arrest and apoptosis. Taken together, we successfully synthesized the first effective CDK12-PARP1 dual inhibitor, which is expected to be an attractive therapeutic strategy for TNBC.

Synthesis of novel benzimidazole clubbed pyrazole heterocycles derivatives as potentially antibacterial agents

Some new derivatives of benzimidazole bearing pyrazole heterocycles 4a–o (2-(1H-benzo[d] imidazol-1-yl)-1- (3, 5-diphenyl-4,5-dihydro-1H- pyrazol-1-yl) ethan-1-one) were synthesized by simple synthetic protocol. The title compounds (4a-o) have been characterized by infrared spectroscopy, 1H and 13C NMR spectroscopy and mass spectroscopy. Anti-bacterial activity of synthesised compounds was carried out in which 3-nitro derivatives 4e and 4o showed good activity against both Gram positive and Gram negative bacterial strain in vitro. Compound 4e was most potent against Gram negative bacteria (E. coli, MIZ= 21mm and E. aerogenes, MIZ = 24mm) in comparison to amoxycilin (E. coli, MIZ= 16mm and E. aerogenes, MIZ = 18mm) while compounds 4i (S. aureus, MIZ = 34mm;) and 4o (S. aureus MIZ = 36mm) were most active against Gram-positive bacteria of the series.

Discovery of Hybrid Thiouracil-Coumarin Conjugates as Potential Novel Anti-SARS-CoV-2 Agents Targeting the Virus's Polymerase "RdRp" as a Confirmed Interacting Biomolecule.

The coronavirus (COVID-19) pandemic, along with its various strains, has emerged as a global health crisis that has severely affected humankind and posed a great challenge to the public health system of affected countries. The replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mainly depends on RNA-dependent RNA polymerase (RdRp), a key enzyme that is involved in RNA synthesis. In this regard, we designed, synthesized, and characterized hybrid thiouracil and coumarin conjugates (HTCAs) by ether linkage, which were found to have anti-SARS-CoV-2 properties. Our in vitro real-time quantitative reverse transcription PCR (RT-qPCR) results confirmed that compounds such as 5d, 5e, 5f, and 5i inhibited the replication of SARS-CoV-2 with EC50 values of 14.3 ± 0.14, 6.59 ± 0.28, 86.3 ± 1.45, and 124 ± 2.38 μM, respectively. Also, compound 5d displayed significant antiviral activity against human coronavirus 229E (HCoV-229E). In addition, some of the HTCAs reduced the replication of SARS-CoV-2 variants such as D614G and B.617.2. In parallel, HTCAs in uninfected Vero CCL-81 cells indicated that no cytotoxicity was noticed. Furthermore, we compared the in silico interaction of lead compounds 5d and 5e toward the cocrystal structure of Suramin and RdRp polymerase with Remdesvir triphosphate, which showed that compounds 5d, 5e, and Remdesvir triphosphate (RTP) share a common catalytical site of RdRp but not Suramin. Additionally, the in silico ADMET properties predicted for the lead HTCAs and RTP showed that the maximum therapeutic doses recommended for compounds 5d and 5e were comparable to those of RTP. Concurrently, the pharmacokinetics of 5d was characterized in male Wistar Albino rats by administering a single oral gavage at a dose of 10 mg/kg, which gave a Cmax value of 0.22 μg/mL and a terminal elimination half-life period of 73.30 h. In conclusion, we established a new chemical entity that acts as a SARS-CoV-2 viral inhibitor with minimal or no toxicity to host cells in the rodent model, encouraging us to proceed with preclinical studies.

Design, synthesis, in-vitro and in-silico studies of chromone‐isoxazoline conjugates as anti‐bacterial agents

A novel series of chromone-isoxazoline conjugates was successfully synthesized by the O-alkylation and 1,3-dipolar cycloaddition reactions using methyl 7‑hydroxy-4H-chromone-3-carboxylate as starting material. The structures of the synthesized hybrid compounds were determined using spectroscopic techniques, and mass spectrometry. The in-vitro antibacterial activity of the target compounds was tested against four bacterial strains, and it was found that compound 5e was active against the strains B. subtilis and P. mirabilis. Theoretical calculations were made at the B3LYP, HF, and M062X level on a 6–31++g(d,p) basis in order to optimize the geometric structures and calculate the geometric and electronic structure parameters of the target compounds. In addition, molecular docking studies were performed to understand and identify the mode of interaction between the hybrid compound 5e and the bacterial proteins of B. subtilis and P. mirabilis. The outcomes revealed that the hybrid compound 5e displayed strong binding affinities within the target receptors’ active site. Also, a 100 ns molecular dynamics simulation was used to assess the behavior and stability of the complexes formed between ligand 5e and the bacterial receptors. Lastly, in silico ADMET analyses suggest that the target compounds exhibit favorable pharmacokinetic properties, including significant oral bioavailability.

New proapoptotic chemotherapeutic agents based on the quinolone-3-carboxamide scaffold acting by VEGFR-2 inhibition

In the current study, we designed and synthesized a series of new quinoline derivatives 10a-p as antiproliferative agents targeting cancer through inhibition of VEGFR-2. Preliminary molecular docking to assess the interactions of the designed derivatives with the binding site of VEGFR-2 (PDB code: 4ASD) displayed binding poses and interactions comparable to sorafenib. The synthesized compounds exhibited VEGFR-2 inhibitory activity with IC50 ranging from 36 nM to 2.23 μM compared to sorafenib (IC50 = 45 nM), where derivative 10i was the most potent. Additionally, the synthesized derivatives were evaluated in vitro for their cytotoxic activity against HepG2 cancer cell line. Seven compounds 10a, 10c, 10d, 10e, 10i, 10n and 10o (IC50 = 4.60, 4.14, 1.07, 0.88, 1.60, 2.88 and 2.76 μM respectively) displayed better antiproliferative activity than sorafenib (IC50 = 8.38 μM). Compound 10i was tested against Transformed Human Liver Epithelial-2 normal cell line (THLE-2) to evaluate its selective cytotoxicity. Furthermore, 10i, as a potent representative of the series, was assayed for its apoptotic activity and cell cycle kinetics’ influence on HepG2, its effects on the gene expression of VEGFR-2, and protein expression of the apoptotic markers Caspase-7 and Bax. Compound 10i proved to have a potential role in apoptosis by causing significant increase in the early and late apoptotic quartiles, a remarkable activity in elevating the relative protein expression of Bax and Caspase-7 and a significant reduction of VEGFR-2 gene expression. Collectively, the obtained results indicate that compound 10i has a promising potential as a lead compound for the development of new anticancer agents.

Design, synthesis, and biological studies of the new cysteine-N-arylacetamide derivatives as a potent urease inhibitor.

Inhibition of Helicobacter pylori urease is an effective method in the treatment of several gastrointestinal diseases in humans. This bacterium plays an important role in the pathogenesis of gastritis and peptic ulceration. Considering the presence of cysteine and N-arylacetamide derivatives in potent urease inhibitors, here, we designed hybrid derivatives of these pharmacophores. Therefore, cysteine-N-arylacetamide derivatives 5a-l were synthesized through simple nucleophilic reactions with good yield. In vitro urease inhibitory activity assay of these compounds demonstrated that all newly synthesized compounds exhibited high inhibitory activity (IC50 values = 0.35-5.83 μM) when compared with standard drugs (thiourea: IC50 = 21.1 ± 0.11 μM and hydroxyurea: IC50 = 100.0 ± 0.01 μM). Representatively, compound 5e with IC50 = 0.35 μM was 60 times more potent than strong urease inhibitor thiourea. Enzyme kinetic study of this compound revealed that compound 5e is a competitive urease inhibitor. Moreover, a docking study of compound 5e was performed to explore crucial interactions at the urease active site. This study revealed that compound 5e is capable to inhibit urease by interactions with two crucial residues at the active site: Ni and CME592. Furthermore, a molecular dynamics study confirmed the stability of the 5e-urease complex and Ni chelating properties of this compound. It should be considered that, in the following study, the focus was placed on jack bean urease instead of H. pylori urease, and this was acknowledged as a limitation.

New Approaches for the Synthesis N-alkylated Benzo[b]thiophene Derivatives together with their Antiproliferative and Molecular Docking Studies.

2-Amino thiophene derivatives are important compounds not only for their uses in many heterocyclic reactions but also due to their wide range of pharmaceutical and biological activities. The aim of this work was to explore a number of new heterocyclic derivatives, studying their inhibitions toward cancer cell lines and studying their structure activity relation ship. Alkylation of 2-amino-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carbonitrile was achieved through its reaction with chloroacetone and 2-bromo-1-(4-aryl)ethanone derivatives to give compounds 3 and 11a-c. The produced compoumds were subjected to further heterocylization reactions and cytotoxic evaluation against the three cancer cell lines MCF-7, NCI-H460 and SF-268, together with the normal cell line WI 38. Further evaluations were obtained through studying their inhibitions against cancer cell lines classified according to the disease. Anticancer screening against hepatocellular carcinoma HepG2 and cervical carcinoma HeLa cell lines for all compounds together with the molecular docking of 12c, 12d, 12e and 12f were studied. Anti-proliferative evaluations and inhibitions for all of the synthesized compounds showed that many compounds exhibited high inhibitions. Toward the three cancer cell lines, compounds 3, 5a, 7a, 9a, 9b, 11b, 12b, 12d, 12e, 12f, 14c, 14e, 14f, 15e, 15f, 16e, 16f, 17c, 18b, 22a and 22c were the most cytotoxic compounds. The high activities of some compounds were attributed to the presence of the electronegative CN and or Cl groups within the molecule. Most of the tested compounds exhibited inhibitions higher than the reference doxorubicin toward hepatocellular carcinoma HepG2 and cervical carcinoma HeLa cell lines. The score of binding energy of compounds 12c, 12d, 12e and 12f was close to the reference Foretinib which appeared through the molecular docking results of such compounds.

Synthesis and Evaluation of Some Sulfonamide-Substituted of 1,3,5-Triphenyl Pyrazoline Derivatives as Tyrosinase Enzyme Inhibitors

Pyrazoline is well-known as heterocycles compound that can exhibit many biological effects. In this work, we synthesized a series of sulfonamide-substituted 1,3,5-triphenyl pyrazoline compounds as a promising tyrosinase inhibitor agent. These compounds prepared by multicomponent reaction of corresponding aldehyde, ketone, and hydrazine using seal-vessel reactor. Pyrazolines compound were tested for their tyrosinase inhibitor activity through in vitro assay. The test result found that compound 4c, 4d, and 4e possessed better tyrosinase inhibitory activity compared to the reference drug, kojic acid. Compound 4c exhibited the strongest tyrosinase inhibitory effect with an IC50 value of 30.14 µM. The results suggested that hydroxyl and methoxy substituent at para position are preferable. Furthermore, molecular docking studies result match the pattern of in vitro assay where the compound will provide a stronger binding interaction and lower binding free energies.

Discovery of novel 2-(trifluoromethyl)quinolin-4-amine derivatives as potent antitumor agents with microtubule polymerization inhibitory activity

In this work, a series of 2-(trifluoromethyl)quinolin-4-amine derivatives were designed and synthesized through structural optimization strategy as a microtubule-targeted agents (MTAs) and their cytotoxicity activity against PC3, K562 and HeLa cell lines were evaluated. The half maximal inhibitory concentration (IC50) of 5e, 5f, and 5o suggested that their potency of anti-proliferative activities against HeLa cell lines were better than the combretastatin A-4. Compound 5e showed the higher anti-proliferative activity against PC3, K562 and HeLa in vitro with IC50 values of 0.49 µM, 0.08 µM and 0.01 µM, respectively. Further mechanism study indicated that the representative compound 5e was new class of tubulin inhibitors by EBI competition assay and tubulin polymerization assays, it is similar to colchicine. Immunofluorescence staining revealed that compound 5e apparently disrupted tubulin network in HeLa cells, and compound 5e arrested HeLa cells at the G2/M phase and induced cells apoptosis in a dose-dependent manner. Molecular docking results illustrated that the hydrogen bonds of represented compounds reinforced the interactions in the pocket of colchicine binding site. Preliminary results suggested that 5e deserves further research as a promising tubulin inhibitor for the development of anticancer agents.

Design, synthesis and biological evaluation of aryl amino derivatives of pyrido [3,2-d]pyrimidines as anticancer agents

A new bunch of substituted aryl amino derivatives structurally modified pyrido[3,2-d]pyrimidines (10a–j) have been synthesized and evaluated for anticancer effects against PC3 (human prostate), A549 (human lung), MCF-7 (human breast) and Colo-205 (human colon) cancer cell lines by utilizing of MTT procedure. Most of the synthesized compounds were showed anticancer activity good to moderate activities with IC50 values range from 0.013 ± 0.0058 µM to 8.22 ± 5.87 µM, whereas, standard 9 etoposide used as standard drug) showed IC50 values from 0.14 ± 0.017 µM to 3.08 ± 0.135 µM, respectively. Among the synthesized compounds, five compounds 10a, 10b, 10c, 10d and 10e demonstrated more potent activity on all cell lines. Mainly, compound 10e displayed higher anticancer activity.

Synthesis of hydrazinylthiazole carboxylates: a mechanistic approach for treatment of diabetes and its complications.

Aim: The deaths of thousands of people and millions affected by diabetes mellitus triggered us to look for alternative possible solutions to cure diabetes and its complications. Materials & methods: A series of hydrazinylthiazole carboxylates (3a-n) was prepared by cyclocondensation reaction of thiosemicarbazones with ethyl 2-chloroacetoacetate. These compounds were screened for antidiabetic potential through α-amylase inhibition, antiglycation and antioxidant assays. Results & conclusion: Most of the compounds exhibited a promising antidiabetic property. Compounds 3e and 3h showed excellent α-amylase and glycation inhibition properties. The hemolytic assay indicated that all compounds are biocompatible. Docking studies carried out on α-amylase target showed correlation between in vitro inhibition and binding energy.

Design, synthesis, characterization, docking studies of novel 4-phenyl acrylamide-1,3-thiazole derivatives as anti-inflammatory and anti-ulcer agents

A great extent of nitrogen containing heterocyclic moiety comprising sulfur atom is recognized as a valuable combination of therapeutics in medicinal chemistry. In particular, thiazoles analogs play a very significant pharmacological role in many potent biological activities, hence drugs like tiazofurin, abafungin, meloxicam, fanetinole, sulphathiazole and thiamine are well known in market. The incorporation of the thiaazole ring can offer enhanced physical-chemical properties to show a wide scope of targets and diverse biological applications. In this view, the title compounds 7(a-j) were synthesized in good yield. The purified compounds were explained by spectroscopic procedures (FT-IR, 1H NMR, 13CNMR, and LC-MS), and lastly, Among the series of (7a-j), compound (7e) showed maximum selectivity for COX-2 with an IC50 of 8.68±0.31 μM, and the rest of the compounds lies at just below the (7e) which reveals that this compound is quite effective for COX-1 rather than COX-2. The activity found in compound (7e) is attributable to the presence of electron releasing methyl group that has the strongest contact with the active site of H+/K+ ATPase in this study.