Compounds 4d Research Articles

Design, Synthesis, and Evaluation of the Selective and Orally Active LSD1 Inhibitor with the Potential of Treating Heart Failure.

LSD1 has become an appealing target for the development of new pharmacologic agents to treat cardiovascular diseases, including heart failure. Herein, we reported the design, synthesis, and structure-activity relationship of a series of TCP-based derivatives targeting LSD1. Docking studies were employed to successfully elucidate the SAR. Particularly, compound 7d, characterized by low toxicity, demonstrated a high affinity for LSD1 at molecular and cellular levels. It also displayed favorable pharmacokinetic properties for oral dosing (e.g., F = 77.61%), effectively alleviating Ang II-induced NRCFs activation in vitro and reducing pathological myocardial remodeling in TAC-induced cardiac remodeling and heart failure in vivo. Additionally, mechanism studies revealed that suppression of myocardial dysfunction by compound 7d is related to LSD1 inhibition-induced TGFβ signaling pathway repressing. In summary, the current report presents compound 7d as a potent LSD1 inhibitor with the potential for further development as a therapeutic agent for pressure overload-related heart failure.

A click-chemistry based strategy for synthesizing coumarin piperazine analogues: Assessment of anti-tubercular, anti-cancer, anti-inflammatory and antioxidant potentials

In this study, a novel series of coumarin piperazine analogues were synthesized using Click chemistry approach. Thus synthesized compounds (8a-j) were evaluated for their pharmacological potentialities. These compounds subjected for evaluation of their anti-tubercular, anti-cancer, anti-inflammatory, and antioxidant properties. Results revealed that analogues 8b, 8d, 8i and 8h are found to be the promising drug-like candidates against Mycobacterium tuberculosis H37Rv strain exhibiting more potent activity than isoniazid with MIC of 2.24, 1.04, 3.72, 5.35 µM respectively. Furthermore, the compound 8d displayed better anti-inflammatory and antioxidant activity with IC50 values of 66.43 µM and 69.14 µM respectively. Molecular docking studies insights into the binding affinities and interactions with a target protein. The in silico ADME profiles supported their pharmacokinetic viability. Predominantly, compound 8d exhibited anticancer activity with IC50 values of 12.42 µM and 26.16 µM with reference to HeLa and MCF-7respectively by inhibiting acetyl-CoA synthetase. These findings highlight more specifically the compound 8d as a potent anti-cancer agent.

Discovery of Cell-Permeable Allosteric Inhibitors of Liver Pyruvate Kinase: Design and Synthesis of Sulfone-Based Urolithins.

Metabolic dysfunction-associated fatty liver disease (MAFLD) presents a significant global health challenge, characterized by the accumulation of liver fat and impacting a considerable portion of the worldwide population. Despite its widespread occurrence, effective treatments for MAFLD are limited. The liver-specific isoform of pyruvate kinase (PKL) has been identified as a promising target for developing MAFLD therapies. Urolithin C, an allosteric inhibitor of PKL, has shown potential in preliminary studies. Expanding upon this groundwork, our study delved into delineating the structure-activity relationship of urolithin C via the synthesis of sulfone-based urolithin analogs. Our results highlight that incorporating a sulfone moiety leads to substantial PKL inhibition, with additional catechol moieties further enhancing this effect. Despite modest improvements in liver cell lines, there was a significant increase in inhibition observed in HepG2 cell lysates. Specifically, compounds 15d, 9d, 15e, 18a, 12d, and 15a displayed promising IC50 values ranging from 4.3 µM to 18.7 µM. Notably, compound 15e not only demonstrated a decrease in PKL activity and triacylglycerol (TAG) content but also showed efficient cellular uptake. These findings position compound 15e as a promising candidate for pharmacological MAFLD treatment, warranting further research and studies.

DFT studies on N-(1-(2-bromobenzoyl)-4-cyano-1H-pyrazol-5-yl)

In this work, molecular descriptors of N-(1-(2-bromobenzoyl)-4-cyano-1H-pyrazol-5-yl) halogenated benzamides (1a-h) have been computed using a quantum chemical technique through DFT. Prior work involved the synthesis of compounds (1a-h) and the assessment of their anticancer activity on breast, colon, and liver tumors: MCF-7, HCT-116, and HepG-2 cell lines respectively. Since 1a, 1b, and 1d showed the most potential anticancer impact, their ability to inhibit EGFRWT was investigated. Based on the biological data, 1b inhibited EGFRWT the most. According to the docking evaluation, an H-bond with the threonine residue was one of the main non-covalent contacts between 1b and the EGFRWT active site residues. PES, MESP, HOMOs, LUMOs, energy band gap, global reactivity indices [electron affinity (A), ionization energies (I), electrophilicity index (ω), nucleophilicity index (ε), chemical potential (μ), electronegativity (χ), hardness (η), and softness (S)], condensed Fukui functions, NBO, and NCIs are the molecular descriptors of 1a-h that were computed using DFT technique. According to the theoretical investigation results, compounds (1a-h) might have anticancer effects; these findings are consistent with the biological findings from our previous research. Compound 1b had the lowest binding energy, according to an assessment of the binding energies between the threonine and the three most active compounds (1a, 1b, and 1d). This is consistent with the outcomes of the docking study and the biological examination of the influence of 1a, 1b, and 1d on EGFRWT.

Design, Synthesis, and Characterization of Novel Thiazolidine-2,4-Dione-Acridine Hybrids as Antitumor Agents.

This study focuses on the synthesis and structural characterization of new compounds that integrate thiazolidine-2,4-dione, acridine moiety, and an acetamide linker, aiming to leverage the synergistic effects of these pharmacophores for enhanced therapeutic potential. The newly designed molecules were efficiently synthesized through a multi-step process and subsequently transformed into their hydrochloride salts. Comprehensive spectroscopic techniques, including nuclear magnetic resonance (NMR), high-resolution mass spectrometry (HRMS), infrared (IR) spectroscopy, and elemental analysis, were employed to determine the molecular structures of the synthesized compounds. Biological evaluations were conducted to assess the therapeutic potential of the new compounds. The influence of these derivatives on the metabolic activity of various cancer cell lines was assessed, with IC50 values determined via MTT assays. An in-depth analysis of the structure-activity relationship (SAR) revealed intriguing insights into their cytotoxic profiles. Compounds with electron-withdrawing groups generally exhibited lower IC50 values, indicating higher potency. The presence of the methoxy group at the linking phenyl ring modulated both the potency and selectivity of the compounds. The variation in the acridine core at the nitrogen atom of the thiazolidine-2,4-dione core significantly affects the activity against cancer cell lines, with the acridin-9-yl substituent enhancing the compounds' antiproliferative activity. Furthermore, compounds in their hydrochloride salt forms demonstrated better activity against cancer cell lines compared to their free base forms. Compounds 12c·2HCl (IC50 = 5.4 ± 2.4 μM), 13d (IC50 = 4.9 ± 2.9 μM), and 12f·2HCl (IC50 = 4.98 ± 2.9 μM) demonstrated excellent activity against the HCT116 cancer cell line, and compound 7d·2HCl (IC50 = 4.55 ± 0.35 μM) demonstrated excellent activity against the HeLa cancer cell line. Notably, only a few tested compounds, including 7e·2HCl (IC50 = 11.00 ± 2.2 μM), 7f (IC50 = 11.54 ± 2.06 μM), and 7f·2HCl (IC50 = 9.82 ± 1.92 μM), showed activity against pancreatic PATU cells. This type of cancer has a very high mortality due to asymptomatic early stages, the occurrence of metastases, and frequent resistance to chemotherapy. Four derivatives, namely, 7e·2HCl, 12d·2HCl, 13c·HCl, and 13d, were tested for their interaction properties with BSA using fluorescence spectroscopic studies. The values for the quenching constant (Ksv) ranged from 9.59 × 104 to 10.74 × 104 M-1, indicating a good affinity to the BSA protein.

Microwave assisted synthesis, acetylcholinesterase inhibition and molecular docking studies of furo[2,3‐d]pyrido[1,2‐a]pyrimidin‐4‐one derivatives

AbstractA series of phenyl, substituted phenyl and thiophene bearing dihydrofuropyrimidin‐4‐ones (3a‐p) were synthesized by Mn(OAc)3 mediated, microwave irradiated radical cyclizations of 2‐hydroxy‐pyridopyrimidin‐4‐one derivatives (1a‐j) with substituted phenylvinylthiophenes (2a‐c) at 70°C in 2 min. Compounds 3a‐j was obtained between 28% and 66% yields. Molecular structures of 3a‐p were determined by 1H NMR, 13C NMR, 19F NMR, FTIR and HRMS techniques. Inhibitory activity of 3a‐p were evaluated against Acetylcholinesterase (AChE) and inhibition results of these compounds showed that the compounds had good inhibition with IC50 values between 0.52 and 3.77 μM. In addition, molecular docking studies were carried out on the most potent inhibitory compounds 3d (IC50 = 0.64 μM), 3p (IC50 = 0.52 μM) and standart drug Donepezil. The binding energies for 3d, 3p and Donepezil are −9.12, −10.08 and −12.65 Kcal/mol, respectively. Based on these results, it was determined that, compounds 3d and 3p are promising AChE inhibitors.

FeCl3 induced sonochemical heteroarylation: Synthesis of meridianin alkaloid analogues for their in silico/in vitro evaluation against SIRT1

Meridianins A − G, the indole based marine alkaloids have displayed a diverse range of biological properties including anti-cancer / anti-tumour activities. Based on reported correlation between anticancer activities and SIRT1 inhibition, the meridianin alkaloid analogues were explored as possible inhibitors of SIRT1. The FeCl3 mediated regioselective heteroarylation under ultrasound irradiation was employed for the synthesis of this class of N-heterocycles. The methodology involved CC bond forming reaction between 2-amino-4-chloropyrimidine and indole to afford a library of desired compounds in varied yield depending on nature of substituent present on the reactant indole. Indeed the product yield was decreased when the NO2 or OH or two chloro groups were present on the indole ring. The usefulness of the current approach was demonstrated via functionalization of one of the synthesized compound i.e. Meridianin G under ultrasound. All the synthesized compounds were characterized by 1H and 13C NMR and MS spectral data. When docked into the SIRT1 in silico, promising interactions with this protein were noted for some of the meridianin analogues synthesized in addition to their probable selectivity towards SIRT1 over SIRT2. The common interacting residues of SIRT1 were found to be VAL412, PHE413, ILE347, ALA262, ILE411, HIS363, GLN345, ASN346, ILE270, PHE273 and PHE297. Indeed, the top four compounds e.g. 3b, 3c, 3d and 3f participated in H-bond interactions through their indole “NH” and the primary amino group with ASN346, HIS363 and VAL412 of SIRT1. Correlating the findings of in silico studies, these compounds showed promising inhibition of SIRT1 in vitro with IC50 ∼2.9–3.7 µM when 3f emerged as the best active molecule. The SAR (Structure-Activity-Relationship) analysis suggested high to good activities for the NO2, Cl, Br or MeO group at C-5 of indole ring (due to participation of these groups in H-bonding interaction as noted during the in silico docking studies) whereas a free NH moiety of the indole ring was essential for activity. The in silico and in vitro studies along with ADME predictions suggested that compound 3b, 3c, 3d and 3f could be of further pharmacological interest.

Synthesis, Antimicrobial Evaluation, DFT, in Silico-Docking, and ADMET Investigations of Novel Chromene-Based 2,4-Thiazolidinediones.

Three series of thiazolidinedione (TZD) derivatives (5a-f, 7a-f, and 9a-f) were prepared efficiently. Afterward, the synthesized candidates' antibacterial efficacy against both gram-positive and gram-negative bacteria was assessed. Compounds 7c, 7d, and 7f had values comparable to that of ampicillin, a reference antibiotic, whereas compounds 5c, 5d, and 7e exhibited the greatest values (23.0±1.0, 27.7±0.6, and 20.0±1.0, respectively) against gram-positive bacteria (Staphylococcus aureus). The optimal structure of the produced molecules was determined by DFT computing. To assess the binding energy and elucidate the interaction between the potential candidates and different proteins, in silico docking is employed. ADMET analysis to assess the synthesized compounds' toxicity, metabolism, excretion, distribution, and absorption.

Biocatalyst mediated green approach for 1,8-dioxo-octahydroxanthenes: SCXRD, Hirshfeld analysis and DFT studies as inhibitors of HIV reverse transcriptase

AIDS, caused by human immunodeficiency virus (HIV) is persistent on being one among the deadliest disease of all time. It destroys the immune system of the body and there is currently no effective cure for this. In this regard, in continuation to our studies on green catalysts, more efficient, constructive, and environmentally sustainable protocols for the synthesis of xanthene and its derivatives as HIV Reverse Transcriptase inhibitors were developed with the use of biocatalyst via baker's yeast that explores a viable approach on expanding environmental challenges and enlightens the superiority and exclusivity of this protocol. The current approach manifests numerous notable advantages that include ease of preparation, handling and benignity of the catalyst, low cost, green reaction conditions, facile workup, excellent yields (87–96 %) with extreme purity. The title compounds were docked on the crystal structure of a catalytic complex of HIV-1 reverse transcriptase (PDB: 1RTD). The C-score values achieved in the range 6.68–3.05 suggest that docking analysis was propitious signifying the review of all the forces of interaction between the ligand and the protein. The crystal studies and DFT analysis of compound 3d correlate the optimized geometrical features with empirically accessible XRD data.

Development of Novel N-Acylhydrazone Derivatives with High Anti-obesity Activity and Improved Safety by Exploring the Pharmaceutical Properties of Aldehyde Group.

The discovery of effective and safe antiobesity agents remains a challenging yet promising field. Our previous studies identified Bouchardatine derivatives as potential antiobesity agents. However, the 8a-aldehyde moiety rendered them unsuitable for drug development. In this study, we designed two series of novel derivatives to modify this structural feature. Through a structure-activity relationship study, we elucidated the role of the 8a-aldehyde group in toxicity induction. We identified compound 14d, featuring an 8a-N-acylhydrazone moiety, which exhibited significant lipid-lowering activity and reduced toxicity. Compound 14d shares a similar lipid-lowering mechanism with our lead compound 3, but demonstrates improved pharmacokinetic properties and safety profile. Both oral and injectable administration of 14d significantly reduced body weight gain and ameliorated metabolic syndrome in diet-induced obese mice. Our findings identify 14d as a promising antiobesity agent and highlight the potential of substituting the aldehyde group with an N-acylhydrazone to enhance drug-like properties.

Microwave-assisted synthesis of novel pyrazolyl sulfones and their antimicrobial evaluation and time-resolved photoluminescence studies

This article reports an efficient and practical microwave-assisted MMPP-promoted synthesis of novel pyrazolyl sulfones from the corresponding 4-(alkyl/cycloalkylthio)-1H-pyrazoles. The reaction of 4-(alkyl/cycloalkylthio)-1H-pyrazoles with magnesium bis(monoperoxyphthalate)hexahydrate (MMPP) as an oxidizing agent afforded the corresponding 4-(alkyl/cycloalkylsulfonyl)-1,3-disubstituted-1H-pyrazoles in 85–95% yield. This method's benefits include its straightforward operation, simple workup, and use of an inexpensive, halogen-free MMPP oxidant that is easy to use and reasonably stable. All synthesized pyrazolyl sulfones were examined against bacterial and fungal strains, and notable antimicrobial activity was demonstrated by a few of the compounds. In order to investigate the prospect of connecting compounds with the highest yield and antimicrobial activity with their opto-electronic properties, time-resolved photoluminescence investigations for compounds 5a, 5b, and 5d were conducted. The tunable spectrum was observed in the micro-second time domain in all three cases, with fluorescent lifetime found higher in the compound having methyl group, intermediate with phenyl group, and lowest with the p-nitrophenyl group. Our procedures will encourage additional research into the valuable properties of pyrazolyl sulfones now that they are widely available with the structural complexity illustrated here.

Drug Design, In Silico-Profiling of New Pyrrole Derivatives: Promising Anticancer Agents Against Acute Myeloid Leukemia

Molecular docking simulation and synthesis of five compounds of N2, N4-bis (2-(4-substituted phenyl)-4-oxothiazolidin-3-yl)-3,5-dimethyl-1H-pyrrole-2,4-dicarboxamide was carried out to evaluate their theoretical binding affinities, targeting acute myeloid leukemia (AML). The chemical structure of the molecules was accurately drawn using ChemDraw Professional 19.1 software. The designed compounds were evaluated for their selectivity towards FLT3's ATP pocket (PDB ID:6JQR) in comparison with the reference ligand (Gilteritinib) by using GOLD suite from the Cambridge Crystallographic Data Centre (CCDC) software (Version 2021.2.0). All the designed compounds exhibited good binding energies with the receptor active pocket and had promising activity. Compounds 2E and 3E showed the highest PLP Fitness (83.30, 80.86 respectively) and it is higher than that of Gilteritinib (71.91). In-silico ADME and drug-likeness studies were performed by using the Swiss ADME server. The results showed that most of the designed compounds expected to be absorbed from the GIT. Compounds 2B-E have high expected GI absorption. All the investigated compounds have no predicted BBB penetration. Additionally, compounds 2A, 2C, 2D, and 3A are not a substrate to P-gps which may indicate a lower expected incidence of resistance by cancer cells in vitro studies. Finally, all of the investigated compounds are not considered to inhibit CYP1A2 enzyme, except for compounds 2A and 3D.

Discovery of pyridoquinoxaline-based new P-gp inhibitors as coadjutant against Multi Drug Resistance in cancer

Multi-drug resistance (MDR) is a serious challenge in contemporary clinical practice and is mostly responsible for the failure of cancer medication therapies. Several experimental evidence links MDR to the overexpression of the drug efflux transporter P-gp, therefore, the discovery of novel P-glycoprotein inhibitors is required to treat or prevent MDR and to improve the absorption of chemotherapy drugs via the gastrointestinal system. In this work, we explored a series of novel pyridoquinoxaline-based derivatives designed from parental compounds, previously proved active in enhancing anticancer drugs in MDR nasopharyngeal carcinoma (KB). Among them, derivative 10d showed the most potent and selective inhibition of fluorescent dye efflux, if compared to reference compounds (MK-571, Novobiocin, Verapamil), and the highest MDR reversal activity when co-administered with the chemotherapeutic agents Vincristine and Etoposide, at non-cytotoxic concentrations. Molecular modelling predicted the two compound 10d binding mode in a ratio of 2:1 with the target protein. No cytotoxicity was observed in healthy microglia cells and off-target investigations showed the absence of CaV1.2 channel blockade. In summary, our findings indicated that 10d could potentially be a novel therapeutic coadjutant by inhibiting P-gp transport function in vitro, thereby reversing cancer multidrug resistance.

Novel antipyrine substituted 4-thiazolidinones: Synthesis, DNA binding and topoisomerase inhibition activities, and in-silico studies

In this study, we report the synthesis and characterization of novel 4-thiazolidinones containing antipyrine (3a-e) derived from the starting compounds of Schiff bases (2a-e). The Schiff bases were synthesized using aldehydes of natural origin, such as citronellal, cuminaldehyde, 2-thiazolecarboxaldehyde, 5-methylfurfural, and syringaldehyde. Their FTIR spectra revealed the enol- tautomeric solid-state structures of compounds 3b and 3d. The pUC18 plasmid DNA binding specificity and capacity of the compounds to catalytically generate topoisomerase I activity were also examined using agarose gel electrophoresis. The compounds induced changes in DNA mobility and showed a topoisomerase I inhibitory effect at all doses. 4-Thiazolidinones had a higher affinity in DNA and topoisomerase I than the Schiff bases. DNA binding and topoisomerase I activities were most effective at low concentration (6 μM) for the compounds of Schiff bases 2a, d, and 4-thiazolidinones 3a, d. Furthermore, this study presents computational methods for addressing the molecules’ drug-like properties. 2a, d, and 3a, d Compounds were used as representative of the most bioactive among the newly synthesized molecules in in-silico studies. The web tools of ADMETlab, SwissADME, OSIRIS, and the BOILED-Egg method were used to conduct in-silico biological studies involving ADME prediction, BBB penetration, gastrointestinal absorption, and toxicity studies. The ADME profile of the query compounds gets within the range of applicability and is at an appropriate level. In-silico studies revealed that compounds 2a, d, and 3a, d are neither hERG blockers nor AMES toxic. However, compounds 2a and 3a have hepatotoxicity.

Synthesis and photodynamic activity of new 5-[(E)-2-(3-alkoxy-1-phenyl-1H-pyrazol-4-yl)ethenyl]-2-phenyl-3H-indoles.

A series of new indole-pyrazole hybrids 8a-m were synthesized through the palladium-catalyzed ligandless Heck coupling reaction from easily accessible unsubstituted, methoxy- or fluoro-substituted 4-ethenyl-1H-pyrazoles and 5-bromo-3H-indoles. These compounds exerted cytotoxicity to melanoma G361 cells when irradiated with blue light (414 nm) and no cytotoxicity in the dark at concentrations up to 10 µM, prompting us to explore their photodynamic effects. The photodynamic properties of the example compound 8d were further investigated in breast cancer MCF-7 cells. Evaluation revealed comparable anticancer activities of 8d in both breast and melanoma cancer cell lines within the submicromolar range. The treatment induced a massive generation of reactive oxygen species, leading to different types of cell death depending on the compound concentration and the irradiation intensity.

Design, Synthesis, and the Biological Evaluation of Some New Fused Thiazolotriazine Derivatives

Thiazolotriazine is an essential medicinal chemistry molecule due to its biological properties, particularly antifungalactivity. Antifungal drug resistance is rising worldwide, necessitating the development of innovative, safer, and more effectiveantifungals. This study intended to uncover safer and more effective thiazolotriazine antifungals. ProTox II software was employedto forecast the toxicity of the designed thiazolotriazines. The pharmacokinetic parameters were calculated using the Swiss-ADMEdatabase. The Molecular Operating Environment software (2019.0102 version) was employed for the docking studies utilizing 14-α-demethylase protein (PDB ID: 3LD6). Compounds 4c, 4d, and 4e were prepared and evaluated for in vitro antifungal activity.The computational studies revealed compounds 4a, 4b, 5b, 5c, 6b, 6c and 6d as carcinogenic; 4a, 4b, 4c, 4d and 4e demonstratedbetter pharmacokinetic behaviour; and docking results of 4c, 4d, and 4e were superior than fluconazole (FLU). The moleculardocking studies establish 4c, 4d, and 4e as SDM inhibitors, suggesting a mechanism similar to FLU and ketoconazole (KET). Theantifungal activity evaluation revealed 4d (MIC = 6.25 μg/ml) as a more potent antifungal agent than KET (MIC = 12.5 μg/ml) andFLU (MIC = 12.5 μg/ml). Compounds 4c and 4e showed equal antifungal activity to KET (MIC = 12.5 μg/ml) and FLU (MIC = 12.5μg/ml). Compounds 4c, 4d, and 4e displayed encouraging antifungal activity with a favorable safety profile. Assessing the broadspectrum of 4c, 4d, and 4e against various pathogenic fungi, including resistant forms, is recommended.

Preliminary evaluation of antiproliferative and apoptotic activities of novel indolin-2-one derivatives.

Indole-based agents are frequently used in targeted or supportive therapy of several cancers. In this study, we investigated the anticancer properties of originally synthesized novel indolin-2-one derivatives (6a-d) against Malignant Mesothelioma, Breast cancer, and Colon Cancer cells. Our results revealed that all derivatives were effectively delayed cell proliferation by inhibiting the ERK1/2, AKT, and STAT3 signaling pathways in a concentration-dependent manner. Additionally, these variants induced cell cycle arrest in the S phase, accompanied by elevated levels of p21 and p27 expressions. Derivatives also initiated mitochondrial apoptosis through the upregulation of Bax and downregulation of Bcl-2 proteins, leading to the activation of caspase 3 and PARP cleavage in exposed cells. Remarkably, three of the indolin-2-one derivatives displayed significant selectivity towards Breast and Colon Cancer cells, with compound 6d promising as the most potent and wide spectral one for all cancer cell lines.

Design and synthesis of new nicotinamide derivatives generated via Suzuki Miyaura coupling as potential anticancer hits targeting pancreatic cancer cell line MIA PaCa-2

Pancreatic cancer is one of the most fatal malignancies with low survival rate and spreads asymptomatically due to the intensive involvement and expression of PARP1 protein. Nicotinamide is recognised as an efficient ring system in the treatment of pancreatic cancer because of its uses in both cellular and biological processes. In this investigation, 3-methoxyphenyl nicotinamide derivatives were synthesised utilizing a palladium-catalysed Suzuki-Miyaura coupling, and their confirmation has been identified by spectroscopic techniques (HRMS, 1H NMR & 13C NMR). The confirmed compounds (5a-f) were introduced to in-vitro cytotoxic studies using the MTT assay, which demonstrated that 5d and 5f were potent against MIA PaCa-2 cell line with IC50 values of 26±1.21µM and 18.61±0.20µM. The compounds 5d and 5f were also examined against HEK 293 cells, which exhibited a diminished antiproliferative effect with an IC50 values of 82.6µM and 138.07µM, respectively. Consequently, 5d and 5f were found to be safer with reduced antiproliferative effect. The MTT assay results were validated by the molecular docking and ADMET studies, which revealed the binding affinities of compounds 5d and 5f are -9.1 and -9.4 Kcal/mol. Overall, the designed and synthesised conjugates 5d and 5f demonstrated a viable lead for the investigation of new chemotherapeutic drugs against pancreatic cancer in this study.

Synthesis and characterization of Azo-Azomethine derivatives bearing thiazole moiety: In vitro antimicrobial, in vitro and in vivo anti-inflammatory, and cytotoxicity assessment, accompanied by computational molecular docking, RDG, ELF, DFT, and MEP analysis

In this study, a novel series of Azo-azomethine derivatives incorporating thiazole moieties (5a-h) were synthesized and thoroughly characterized using NMR (1H and 13C), FT-IR spectroscopy, and ESI-MS methods. The synthesized compounds underwent screening for their antimicrobial, anti-inflammatory (both in vitro and in vivo), and cytotoxic activities. Notably, compound 5d exhibited significant activity against S. aureus and S. epidermidis, with minimum inhibitory concentration (MIC) values as low as 20 μg/L. Additionally, compound 5d demonstrated the most potent anti-inflammatory activity both in vitro (84.72%) and in vivo. Furthermore, molecular analyses including RDG, ELF, DFT, and MEP were conducted to investigate molecular interactions, electron distribution, electronic configuration, and electrostatic potential, thus facilitating a deeper understanding of the molecular characteristics and aiding in the refinement and design of these molecules. Moreover, the compounds' efficacy against bacterial proteins was assessed through molecular docking calculations. Utilizing the PASS and pkCSM platforms, an examination of the compounds' bioactivity regulation and physicochemical attributes was conducted, highlighting their potential as prospective novel active agents.

Novel Amide Functionalized Trifluoromethyl thieno[2,3-b]pyridine Derivatives: Anti-cancer Activity and Molecular Docking Studies

Abstract: Our primary research objective is to create and formulate small ring heterocycles with enhanced biological efficacy. Amide functionalized trifluoromethyl thieno[2,3-b]pyridine derivatives as a series were prepared starting from reaction between 1,3 di-ketone and thiocyanoacetamide and obtained pyridine 3. Compound 3 reacts with bromoethyl acetate and obtained compound 4, further compound 4 on reaction with diverse substituted aromatic and aliphatic amines to get amide derivatives 5a-d, 6a-d and 7a-h. All the final compounds evaluated for anti cancer activity against four human cancer cell lines such as ‘HeLa - Cervical cancer (CCL-2); COLO 205- Colon cancer (CCL- 222); HepG2 - Liver cancer (HB-8065); MCF7 - Breast cancer (HTB-22)’ and promising compounds 7d, 7e and 7f have been identified. For compounds 7d, 7e and 7f molecular docking interactions have been identified.