Compounds 4g Research Articles

Synthesis and evaluation of sulfonamide derivatives of quinoxaline 1,4-dioxides as carbonic anhydrase inhibitors.

A series of sulfonamide-derived quinoxaline 1,4-dioxides were synthesized and evaluated as inhibitors of carbonic anhydrases (CA) with antiproliferative potency. Overall, the synthesized compounds demonstrated good inhibitory activity against four CA isoforms. Compound 7g exhibited favorable potency in inhibiting a CA IX isozyme with a K i value of 42.2 nM compared to the reference AAZ (K i = 25.7 nM). Nevertheless, most of the synthesized compounds have their highest activity against CA I and CA II isoforms over CA IX and CA XII. A molecular modeling study was used for an estimation of the binding mode of the selected ligand 7g in the active site of CA IX. The most active compounds (7b, 7f, 7h, and 18) exhibited significant antiproliferative activity against MCF-7, Capan-1, DND-41, HL60, and Z138 cell lines, with IC50 values in low micromolar concentrations. Moreover, derivatives 7a, 7e, and 8g showed similar hypoxic cytotoxic activity and selectivity compared to tirapazamine (TPZ) against adenocarcinoma cells MCF-7. The structure-activity relationships analysis revealed that the presence of a halogen atom or a sulfonamide group as substituents in the phenyl ring of quinoxaline-2-carbonitrile 1,4-dioxides was favorable for overall cytotoxicity against most of the tested cancer cell lines. Additionally, the presence of a carbonitrile fragment in position 2 of the heterocycle also had a positive effect on the antitumor properties of such derivatives against the majority of cell lines. The most potent derivative, 3-trifluoromethylquinoxaline 1,4-dioxide 7h, demonstrated higher or close antiproliferative activity compared to the reference agents, such as doxorubicin, and etoposide, with an IC50 range of 1.3-2.1 μM. Analysis of the obtained results revealed important patterns in the structure-activity relationship. Moreover, these findings highlight the potential of selected lead sulfonamides on the quinoxaline 1,4-dioxide scaffold for further in-depth evaluation and development of chemotherapeutic agents targeting carbonic anhydrases.

Synthesis and biological research of new imidazolone-sulphonamide-pyrimidine hybrids as potential EGFR-TK inhibitors and apoptosis-inducing agents.

Development of new effective EGFR-targeted antitumor agents is needed because of their clinical significance. A new series of imidazolone-sulphonamide-pyrimidine hybrids was designed and synthesized as modified analogs of some reported EGFR inhibitors. The cytotoxic activity of all the synthesized hybrids was investigated against the breast MCF-7 cancerous cell line using doxorubicin (Dox) as a positive control. 4-(Furan-2-ylmethylene)imidazolone-sulphonamide-pyrimidine 6b had the best potent activity against MCF-7 cells with IC50 result of 1.05 μM, which was better than Dox (IC50 = 1.91 μM). In addition, mechanistic studies revealed the ability of compounds 5g, 5h and 6b to inhibit EGFR kinase. Cell cycle analysis revealed that compound 6b can halt MCF-7 cells at the G1 phase with a concomitant decrease in cellular percentage at the S and G2/M phases. This compound produced a noticeable rise in the proportion of apoptotic cells with regard to the untreated control. Furthermore, the effects of hybrid 6b on the expression levels of pro-apoptotic Bax and pro-survival Bcl2 were assessed. The results showed that this compound upregulated the level of Bax expression as well as declined the expression value of Bcl-2 with regard to the untreated control.

Skin delivery of synthetic benzoyl pterostilbenes suppresses atopic dermatitis-like inflammation through the inhibition of keratinocyte and macrophage activation

Atopic dermatitis (AD) is one of the most common skin autoimmune diseases needing continuous anti-inflammatory management. Pterostilbene is reported to exhibit anti-inflammatory activity with higher bioavailability and stability than its parent compound, resveratrol. In this study, a series of synthetic pterostilbene analogs were designed by the hybridization of pterostilbene with chalcones or benzoyl chloride. Seventeen analogs derived from pterostilbene were synthesized with differences in the positions of hydroxyl, methoxyl, or fluoro moieties. These compounds were screened by the inhibitory effect on the overexpressed Th2-associated cytokines/chemokines in the activated human keratinocytes (HaCaT). The anti-IL-5 and anti-CCL5 activity of these compounds led to the identification of three effective compounds: 3a ((E)− 4-(3,5-dimethoxystyryl)phenyl benzoate), 3d ((E)− 4-(3,5-dimethoxystyryl)phenyl 2-methoxybenzoate), and 3g ((E)− 4-(3,5-dimethoxystyryl)phenyl 2-fluorobenzoate). These benzoyl pterostilbenes also significantly decreased Th1/Th17-associated proinflammatory mediators in the activated macrophages (differentiated THP-1). The result showed that the conditioned medium of benzoyl pterostilbene-treated macrophages reduced the phosphorylated STAT3 in the keratinocytes, indicating the blockade of crosstalk between resident and immune cells. Compounds 3d and 3g generally showed greater skin absorption than 3a. The flux of 3g across barrier-defective skins mimicking the AD skin was 3-fold higher than that of across intact skin. The dinitrochlorobenzene (DNCB)-induced AD mouse model manifested that topical delivery with 3g improved the pathological signs through inhibiting cytokines/chemokines (IL-5, TNF-α, CCL17, and CCL22) and macrophage recruitment. The epidermal thickness was reduced from 76 to 55 µm after topical 3g delivery. The therapeutic activity of 3g was comparable to that of tacrolimus (TAC) used as a positive control. The benzoyl pterostilbenes attenuated the inflammation via the MAPK and c-Jun signaling. Furthermore, this study provided experimental evidence of benzoyl pterostilbene analogs for therapeutic potential on AD.

Synthesis, molecular docking, and molecular dynamic simulation studies of new 1,3,4-thiadiazole derivatives as potential apoptosis inducers in A549 lung cancer cell line

1,3,4-Thiadiazoles are structures that are bioisosteres of 1,3,4-oxadiazole and pyrimidine ring, which are found in the structure of many drugs and anticancer active newly studied derivatives. In the past, high effect profiles have been observed in many molecules created, based on the anticancer effects of the 2-amino-1,3,4-thiadiazole (NSC 4728) molecule and acetazolamide molecules. Focusing on these molecules and evaluating them in terms of mechanistic effects, twelve new N-[5-((3,5-dichlorophenoxy) methyl]-1,3,4-thiadiazole derivatives (3a–3i) were synthesized and their biological activities were investigated in lung cancer cells. The anticancer effects of the compounds were evaluated on the A549 and L929 cell lines. Compound 3f, namely 2-[(5-chlorobenzotiyazol-2-yl)thio]-N-[5-[(3,5-dichlorophenoxy)methyl]-1,3,4-thiadiazol-2-yl]acetamide, showed better activity than cisplatin, exhibiting high inhibitory potency (IC50: <0.98 μg/mL) and selectivity against A549 cell line even at the lowest concentration tested. Compounds 3c, 3f, and 3h with the lowest IC50 values of the compounds exhibited an excellent percentage of apoptosis between 72.48 and 91.95% compared to cisplatin. The caspase-3 activation and mitochondrial membrane potential change of the aforementioned three compounds were also studied. Moreover, matrix metalloproteinase-9 (MMP-9) inhibition potential of all final compounds was also investigated and IC50 values for compounds 3b and 3g were identified as 154.23 and 107.28 µM. Molecular docking and molecular dynamic simulation studies for MMP-9 enzyme inhibition were realized on these compounds and the nitrogen atoms of amide and thiadiazole moieties’ ascertained that they play a key role in chelating with Zn metal, at the same time, (thio)ether moieties allow conformational change resulting in the ligand can make more stable contacts. Communicated by Ramaswamy H. Sarma

Synthesis of novel cyano quinolone derivatives and their antibacterial activities

Seven cyano 4-quinolone derivatives were synthesized 2 (A-G) and the synthesized compound's antibacterial activity was tested. Structural elucidation of the synthesized compounds was carried out by their mass, infrared and N.M.R analysis. Antibacterial activity was evaluated against six bacterial strains e.g. Escherichia coli, Enterococcus faecalis, Staphylococcus aureus, Staphylococcus epidermidis, Salmonella enterica and Pseudomonas aeruginosa. After the analysis of the antibacterial activity, it was inferred that compounds 2C and 2G were found to be more active against Gram-negative and Gram-positive bacteria and are found to be potential candidates for the antibacterial drug. A different approach of replacing the 6th position fluorine of the quinolone ring with the cyanide group was carried out. Compound 2E was found to be the most active with MIC values of 0.0047, 0.0031, 0.0013, 0.0011, 0.0008, 0.012 respectively. This research leads to the development of cyano4-quinolones.

New pyrrolidine-carboxamide derivatives as dual antiproliferative EGFR/CDK2 inhibitors.

Cancer is one of the leading causes of mortality worldwide, making it a public health concern. A novel series of pyrrolidine-carboxamide derivatives 7a-q were developed and examined in a cell viability assay utilizing a human mammary gland epithelial cell line (MCF-10A), where all the compounds exhibited no cytotoxic effects and more than 85% cell viability at a concentration of 50 μM. Antiproliferative activity was evaluated invitro against four panels of cancer cell lines A-549, MCF-7, Panc-1, and HT-29. Compounds 7e, 7g, 7k, 7n, and 7o were the most active as antiproliferative agents capable of triggering apoptosis. Compound 7g was the most potent of all the derivatives, with a mean IC50 of0.90 μM compared to IC50 of 1.10 μM for doxorubicin. Compound 7g inhibited A-549 (epithelial cancer cell line), MCF-7 (breast cancer cell line), and HT-29 (colon cancer cell line) more efficiently than doxorubicin. EGFR inhibitory assay results of 7e, 7g, 7k, 7n, and 7o demonstrated that the tested compounds inhibited EGFR with IC50 values ranging from 87 to 107 nM in comparison with the reference drug erlotinib (IC50 = 80 nM). 7e, 7g, 7k, 7n, and 7o inhibited CDK2 efficiently in comparison to the reference dinaciclib (IC50 = 20 nM), with IC50 values ranging from 15 to 31 nM. The results of inhibitory activity assay against different CDK isoforms revealed that the tested compounds had preferential inhibitory activity against the CDK2 isoform.

Design, synthesis, and biological evaluation of HDAC6 inhibitors targeting L1 loop and serine 531 residue

Histone deacetylases (HDACs) are a group of enzymes that remove acetyl groups from histones, leading to the silencing of genes. Targeting specific isoforms of HDACs has emerged as a promising approach for cancer therapy, as it can overcome drawbacks associated with pan-HDAC inhibitors. HDAC6 is a unique HDAC isoform that deacetylates non-histone proteins and is primarily located in the cytoplasm. It also has two catalytic domains and a zinc-finger ubiquitin binding domain (Zf-UBD) unlike other HDACs. HDAC6 plays a critical role in various cellular processes, including cell motility, protein degradation, cell proliferation, and transcription. Hence, the deregulation of HDAC6 is associated with various malignancies. In this study, we report the design and synthesis of a series of HDAC6 inhibitors. We evaluated the synthesized compounds by HDAC enzyme assay and identified that compound 8g exhibited an IC50 value of 21 nM and 40-fold selective activity towards HDAC6. We also assessed the effect of compound 8g on various cell lines and determined its ability to increase protein acetylation levels by Western blotting. Furthermore, the increased acetylation of α-tubulin resulted in microtubule polymerization and changes in cell morphology. Our molecular docking study supported these findings by demonstrating that compound 8g binds well to the catalytic pocket via L1 loop of HDAC6 enzyme. Altogether, compound 8g represents a preferential HDAC6 inhibitor that could serve as a lead for the development of more potent and specific inhibitors.

Identification of novel sulfathiazole-triazolo-chalcone hybrids as VEGFR-2/EGFR dual inhibitors with antiangiogenic activity and apoptotic induction.

Certain sulfathiazole-triazolo chalcone hybrids were identified as anticancer agents with dual vascular endothelial growth factor receptor-2 (VEGFR-2)/epidermal growth factor receptor (EGFR) kinase inhibitory effect. All of the compounds were evaluated for their cytotoxic activity against the MCF-7 and HepG-2 tumor cell lines. Compounds 11g, 11h, and 11j exhibited the most potent antiproliferative activity against both cancer cell lines, with good safety toward WI-38 normal cells. Thus, they were further assessed for VEGFR-2 inhibitory activity. They have suppressed VEGFR-2 enzyme at IC50 of 0.316, 0.076, and 0.189 µM, respectively in comparison to sorafenib (IC50 = 0.035 µM). EGFR enzyme inhibition was further screened for the most potent inhibitors, 11h and 11j, where they displayed enhanced potency with IC50 of 0.085 and 0.108 µM, respectively, compared to erlotinib (IC50 = 0.037 µM). Compounds 11h and 11j were additionally investigated for inhibition of comparable kinases, PDGFR-β and B-Raf, where results assessed adequate selectivity of both compounds toward the VEGFR-2 and EGFR kinases. Furthermore, the wound healing assay of compound 11h manifested a percent wound closure of 65.18% in MCF-7 cells compared to doxorubicin (58.51%) and untreated cells (97.77%), proving its antiangiogenic activity. The cell cycle assay of MCF-7 cells treated with 11h demonstrated cell cycle arrest at the S phase. Moreover, compound 11h induced apoptosis with a 44-fold increase compared to that induced in the control MCF-7 cells. Molecular docking results of compounds 11h and 11j established their efficacies, and in silico studies showed convenient safety profiles with drug-likeness properties.

Potentially active aspirin derivative to release nitric oxide: In-vitro, in-vivo and in-silico approaches

The series of newer salicylate derivatives incorporating nitroxy functionality were synthesized and evaluated for their potential effect in gastrointestinal (GI) related toxicity produced by aspirin. The synthesized compounds (5a-j) were subjected to %NO (nitric oxide) release study, in-vitro anti-inflammatory potential, % inhibition of carrageenan-induced paw edema and the obtained results were validated by in-silico studies including molecular docking, MD simulations and in-silico ADME (absorption, distribution, metabolism, and elimination) calculations. Compounds 5a (20.86 %) and 5g (18.20 %) displayed the highest percentage of NO release in all the tested compounds. Similarly, 5a and 5h were found to have (77.11 % and 79.53 %) &(78.56 % and 66.10 %) inhibition in carrageenan induced paw edema in animal mode which were relatively higher than ibuprofen (standard used). The obtained results were validated by molecular docking and MD simulations studies. The molecular docking study of 5a and 5h revealed that docking scores were also obtained in very close proximity of −8.35, −9.67 and −8.48 for ibuprofen, 5g and 5h respectively. In MD simulations studies, the calculated lower RMSD (root mean square deviation) values 2.8 Å and 5.6 Å for 5g and 5h, respectively indicated the stability of ligand-protein complexes. Similarly lower RSMF (root mean square fluctuation) values indicated the molecules remained in the active pocket throughout the entire MD simulations run. Further, in-silico ADME calculations were determined and all compounds obey the Lipinski’s rule of five and it was predicted that these molecules would be orally active without any serious toxic effect.

Synthesis of 1,3,4-Thiadiazole Derivatives and Their Anticancer Evaluation.

Thiadiazole derivatives have garnered significant attention in the field of medicinal chemistry due to their diverse pharmacological activities, including anticancer properties. This article presents the synthesis of a series of thiadiazole derivatives and investigates their chemical characterization and potential anticancer effects on various cell lines. The results of the nuclear magnetic resonance (NMR) analyses confirmed the successful formation of the target compounds. The anticancer potential was evaluated through in silico and in vitro cell-based assays using LoVo and MCF-7 cancer lines. The assays included cell viability, proliferation, apoptosis, and cell cycle analysis to assess the compounds' effects on cancer cell growth and survival. Daphnia magna was used as an invertebrate model for the toxicity evaluation of the compounds. The results revealed promising anticancer activity for several of the synthesized derivatives, suggesting their potential as lead compounds for further drug development. The novel compound 2g, 5-[2-(benzenesulfonylmethyl)phenyl]-1,3,4-thiadiazol-2-amine, demonstrated good anti-proliferative effects, exhibiting an IC50 value of 2.44 µM against LoVo and 23.29 µM against MCF-7 after a 48-h incubation and little toxic effects in the Daphnia test.

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

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

Benzylpyrazolyl naphthoquinones as potential VEGFR-2, GPCR and PPAR inhibitors: Synthesis, anti-cancer evaluation, molecular docking and DFT studies

The present study reports the synthesis of benzylpyrazolyl naphthoquinones using nano-Fe3O4 supported Bronsted acidic ionic liquid ([nano-Fe3O4@BenzImi]SO3H) as magnetically retrievable solid acid catalyst. In vitro anti-cancer activity of the synthesized benzylpyrazolyl naphthoquinones have been evaluated against breast cancer cell line (MCF-7) and liver cancer cell line (HepG2). Compound 4h was found to be the most active compounds with IC50 values 0.0436±0.31 µM against MCF 7 cell line whereas compound 4e was displayed highest activity with IC50 values 0.0314±0.16 µM against HepG2 cell line as compared to the standard 5-fluorouracil (0.0384±0.10 and 0.0330±0.09 µM). Furthermore, in silico bioactivity studies revealed that the compounds have significant interactions with the drug targets. The molecular docking studies revealed that the compounds have significant binding affinity with potential receptors such as vascular endothelial growth factor receptor (VEGFR-2), G-protein coupled receptor (GPCR) and peroxisome proliferator-activated receptors (PPAR). The compound 4g has strong hydrogen bond interaction with VEGFR-2 as well as the lowest binding energy (-9.3 kcal/mol−1), similarly, 4c has strong hydrogen bond interaction with in GPCR as well as the lowest binding energy (-7.8 kcal/mol−1) whereas 4a and 4e show strong hydrogen bond interaction with in PPAR as well as lowest binding energy (-10.1 kcal/mol−1 and -10.1 kcal/mol−1) as compared to other compounds. The docking studies revealed that these compounds gets stabilized via hydrogen bonding interactions, van der Waals contacts and electrostatic interactions which were further supported through estimation of HOMO-LUMO energies, ionization potential, electron affinities, dipole moment etc. using density functional theory (DFT) analysis. The work highlights biological significance of benzylpyrazolyl naphthoquinones as a potential anti-cancer reagent.

Design and Evaluation of Synthesized Pyrrole Derivatives as Dual COX-1 and COX-2 Inhibitors Using FB-QSAR Approach.

This study delves into the intricate dynamics of the inflammatory response, unraveling the pivotal role played by cyclooxygenase (COX) enzymes, particularly COX-1 and COX-2 subtypes. Motivated by the pursuit of advancing scientific knowledge, our contribution to this field is marked by the design and synthesis of novel pyrrole derivatives. Crafted as potential inhibitors of COX-1 and COX-2 enzymes, our goal was to unearth molecules with heightened efficacy in modulating enzyme activity. A meticulous exploration of a synthesis library, housing around 3000 compounds, expedited the identification of potent candidates. Employing advanced docking studies and field-based Quantitative Structure-Activity Relationship (FB-QSAR) analyses enriched our understanding of the complex interactions between synthesized compounds and COX enzymes. Guided by FB-QSAR insights, our synthesis path led to the identification of compounds 4g, 4h, 4l, and 4k as potent COX-2 inhibitors, surpassing COX-1 efficacy. Conversely, compounds 5b and 5e exhibited heightened inhibitory activity against COX-1 relative to COX-2. The utilization of pyrrole derivatives as COX enzyme inhibitors holds promise for groundbreaking advancements in the domain of anti-inflammatory therapeutics, presenting avenues for innovative pharmaceutical exploration.

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

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

Synthesis and antifungal activity of 2,4-dihydroxy-5-methylphenyl ethanone derivatives against phytopathogenic fungi in vitro

In an endeavor to pinpoint the structural constituents vital for the biological activity of 2,4-dihydroxy-5-methylphenyl ethanone, a series of its ether derivatives was synthesized and examined for their antifungal activities against five notable phytopathogenic fungi. The bioassay revealed that compounds 2, 3a, 3g, 3j and 3k manifested a broad spectrum of antifungal efficacy. Notably, compound 3g was identified as especially potent, with IC50 values ranging from 16.52 to 37.52 μg/mL, outperforming the standard thiabendazole. The data underscore compound 3g as a prospective candidate for the development of an innovative antifungal agent. A comprehensive structure-activity relationship (SAR) study of the acetophenones was also conducted.

Sonochemical synthesis of New Thiazolidin-4-one derivatives as potent anticancer and antimicrobial agents with Docking design, and Energy gap estimation

Thiazolidin-4-ones have important biological features, which has led to the development of new derivatives employing an efficient ultrasonic method. Schiff base derivatives were synthesized by condensation of 4,4′-diaminophenylmethane with various substituted benzaldehyde. These derivatives are subsequently subjected to cyclization, leading to the formation of thiazolidine-4-ones with favorable yields. The synthesized compounds were characterized using various analytical techniques such as FT-IR, 1H and 13C NMR, HRMS spectroscopy, and CHNS analysis. Thiazolidin-4-ones demonstrated anticancer potential with percentage cell viability at different concentrations (1mM, 3mM, and 5mM) and cell toxicity (1mM, 3mM, and 5mM). The IC50 values of compound 4g were found to be (72.27±1.39, 67.28±1.63, and 63.22±1.82), (36.77±0.11, 32.71±0.31, and 32.71±0.31), and 10.77±0.95, respectively. It is a good result according to the standard. The tested compounds demonstrated remarkable antimicrobial efficacy against bacterial strains like Staphylococcus aureus, Escherichia coli, and the fungal strain Candida albicans. The Minimum Inhibitory Concentrations (MIC) of compound 4g against Staphylococcus aureus, Escherichia coli, and Candida albicans were found to be 0.50±0.027, 0.70±0.040, and 0.80±0.036, respectively, which are comparable to reference medications. Docking design was conducted with the Staphylococcus aureus MurB protein (ID Code: 1HSK) and Novel CDK-5 inhibitor EFP crystal structure with CDK-2 (ID Code: 3IG7) for colon carcinoma HT29. Finally, the energy gaps were estimated by calculating HUMO and LUMO energy levels using the DFT/B3LYP method with the 6-31 G (d, p) basis set.

Novel triazolo pyridine derivatives and their anti cancer activity

A series of novel triazole functionalized trifluoromethyl pyridine derivatives was prepared starting from pyridine 1. Compound 1 on reaction with sulphuric acid gave compound 2 which on chlorination followed by hydrazine hydrate and obtained compound 3 and 4. Compound 4 on reaction with diverse substituted aliphatic and aromatic acid chlorides produced amide derivatives 4a-h and 5a-h. All the final compounds were 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). Promising compounds 4f and 4g were identified.

Synthetic Transformation of 4-fluorobenzoic Acid to 4-fluorobenzohydrazide Schiff Bases and 1,3,4-Oxadiazole Analogs having DPPH Radical Scavenging Potential

Aims: Synthesis of 4-fluorobenzohydrazide Schiff bases and 1,3,4-oxadiazole analogs has a DPPH radical scavenging potential. Background: Synthetic antioxidants are widely used because they are effective and cheaper than natural antioxidants. Based on the literature survey, this present study is mainly focused on the study of the free radical scavenging activity of the Schiff base and oxadiazole motifs. Methods: In this research work, Schiff’s base (4a-4g) and 1,3,4-oxadiazole (5a-5g) derivatives based on 4-fluorobenzoic acid were synthesized through multistep reactions. Initially, 4-fluorobenzoic acid was esterified in the presence of sulphuric acid (H2SO4) in ethanol solvent, and then it was reacted with an excess of hydrazine hydrate to obtain the desired 4-fluorobenzohydrazide. Various aromatic aldehydes were reacted with 4-fluorobenzo hydrazide in the presence of a catalytic amount of acetic acid to obtain the desired hydrazones. Finally, different substituted hydrazones were cyclized in the presence of iodine and potassium carbonate in DMSO to obtain substituted 1,3,4-oxadiazoles. The progress of all reactions was checked using thin-layer chromatography. The compounds were recrystallized from ethanol with good yield. The synthesized compounds were characterized with the help of EI-MS and 1H-NMR spectroscopy. Results: The synthesized Schiff bases (4a-4g) and oxadiazole derivatives (5a-5g) of 4-fluorobenzoic acid demonstrated good free radical scavenging activity. Among the series, Compound 4f (IC50 = 25.57 ± 7.41 μM), showed comparable activity when compared with the standard Vitamin C (IC50 = 19.39 ± 12.57 μM). Similarly Compound 4a (IC50 = 40.90 ± 1.92 μM), 4b (IC50 = 34.77 ± 1.03 μM), 4c (IC50 = 90.2 ± 2.90 μM), 4e (IC50 = 78.62 ± 9.64 μM), 4g (IC50 = 80.65 ± 1.80 μM), 5a (IC50 = 52.67 ± 4.98 μM) and 5f (IC50 = 89.45 ± 9.11 μM) showed moderate antioxidant activity. Furthermore compounds, 4d (IC50 = 102.55 ± 10.4 μM), 5b (IC50 = 123.76 ± 12.34 μM), 5d (IC50 = 701.62 ± 1.06 μM), and 5e (IC50 = 102.87 ± 7.98 μM) displayed less significant anti-oxidant potential, while compounds 5c and 5g were found inactive. Conclusion: Schiff’s base (4a-4g) and substituted 1,3,4-oxadiazole (5a-5g) derivatives based on 4- fluorobenzoic acid scaffolds were synthesized using standard pathways. All compounds were structurally characterized through EI-MS and 1H-NMR spectroscopy and evaluated for their in vitro DPPH free radical scavenging activity. In-vitro study reveals that the newly prepared derivatives of 4-fluorobenzoic acid have potent antioxidant potential. Whereas compound 5c and 5g were found inactive, this study has recognized a series of potential molecules as antioxidant agents and is useful in the field of medicinal chemistry.

Efficient, Green One-Pot Synthesis of Antimicrobial Agents: Functionalized DPTS Catalyst for the Preparation of 2-Amino-4-Aryl-5-Oxo-4HChromene- 3-Carbonitriles, with Theoretical Calculations

Background: In the search for a new and effective synthetic approach to bio-logically chromene-derived compounds, a series of 2-amino-7, 7-dimethyl-5-oxo-4H-tetrahydrochromene-3-carbonitrile derivatives (4a-i) were synthesized. This synthesis involved the use of 4-(dimethylamino)pyridiniump-toluenesulfonate (DPTS) as a catalyst in an aqueous medium. Additionally, the relative stability between isomers was investigated using DFT/B3LYP calculations. Methods: The target compounds were synthesized through a multicomponent reaction of 5,5-dimethyl-1,3-cyclohexanedione (dimedone) 1, various arylaldehydes (2a-i), and malononitrile 3 in water and were recrystallized in ethanol. The reaction was promoted using DPTS, which is a low-toxic, inexpensive, commercially available, and easy-to-handle catalyst. Results: The catalytic activity of DPTS was investigated in a condensation reaction conducted in an aqueous medium at room temperature. All synthesized compounds displayed considerable antimicrobial activities against human pathogenic bacteria and fungi. Conclusion: The developed synthetic protocol demonstrates energy efficiency, shorter reaction time, environmental friendliness, high product yields with purity, and scalability to gram-scale synthesis. DPTS proved to be a valuable contribution to the field of organocatalysis. The synthesized compounds were screened for in vitro antimicrobial activities, demonstrating varying potency against the microbial strains. Compound 4h exhibited the most potent activity with a zone of inhibition (ZOI) measuring 15 mm against E.coli. This was followed by compounds 4b, 4d, 4f, and 4g, which displayed a ZOI of 12 mm. Furthermore, the antifungal results revealed promising anticandidal activity for compounds 4b, 4e, and 4h, with a lower minimum inhibitory concentration (MIC) of 0.031 mg/ml. In addition, molecular electrostatic potential (MEP) mapping, reactivity indices such as electronegativity, electrophilic index, softness, and hardness, as well as frontier molecular orbitals (HOMO-LUMO), were used to provide further evidence regarding the stability and reactivity of the synthesized products.

Synthesis and Biological Evaluation of 1-Substituted (R)-6-(2?-Cyano-1?-Pyrrolidin-yl)-4-(3?- Hydroxyadamantan-1?-yl)-3-phenyl-1,2,4-triazines

A series of various 1-substituted (R)-6-(2?-cyano-1?-pyrrolidin-yl)-4-(3?-hydroxy adamantan-1?-yl)-3-phenyl- 1,2,4-triazines (5a-i) was synthesized by the reaction of (R)-6-(2?-cyano-1?-pyrrolidin-yl)-4-(3?-hydroxy adamantan-1?- yl)-3-phenyl-1,4-dihydro-1,2,4-triazine (4) with heterocyclic halogenated compounds (R-X) in the presence of potassium carbonate. All the synthesized compounds were evaluated biologically and also determined In vitro cytotoxicity of compounds 5a, 5c, 5d, 5e, 5g, and 5h against human cervical cancer cell line (HeLa). Among all the synthesized compounds, some compounds exhibited potent antimicrobial activity as well as cytotoxicity.. KEYWORDS :1,2,4-Triazine, Adamantanol, Biological activities, Pyrrolidine.