Compounds 4i Research Articles

Design, synthesis, in silico studies, and antidiabetic activity of several sulfanilamide incorporated 2,3-disubstituted thiazolidin-4-ones

A panel of 2,3-disubstituted thiazolidin-4-ones 4a-n was synthesised from Schiff bases 3a-n derived from sulfanilamide, by reaction with thioglycolic acid. The compounds were characterised by means of IR, NMR, and Mass spectral data. Compounds 4a-n were screened for DPPH scavenging assay and compounds 4e, 4h, 4i, and 4n exhibited moderate activity. Compounds 4e, 4h, and 4i were tested at 200 mg/kg and 4e at 50 mg/kg b.w. orally for antidiabetic activity in fructose induced diabetic rats. They exhibited significant antidiabetic activity compared to the control group. Pioglitazone was used as a standard drug. The tested compounds exhibited better and ignificant serum cholesterol lowering activity when compared with the control and standard groups. They also reduced the triglyceride level after the 21st day; however, it was insignificant when compared to the control group. Compound 4n displayed the highest binding energy when docked with PPAR-γ followed by compounds 4e, 4h, and 4i when compared to pioglitazone. The physicochemical, drug likeness and ADME properties of the title compounds were found to be satisfactory.

Design, synthesis, and evaluation of new anti-inflammatory natural products amide derivatives endowed with anti-blood cancer activity towards development of potential multifunctional agents against hematological cancers

New amide derivatives of the natural product 5,6,7-trimethoxyflavanone were designed as multifunctional antiproliferative molecules against blood cancer and the associated inflammatory conditions. The targeted compounds were synthesized efficiently in three linear steps employing known chalcone starting materials. Compounds 2h, 2i, 2l, 2t, 2v and 2x having bromo or nitro substituted-phenyl rings elicited potential inhibitory effects on macrophages production of nitric oxide, PGE2 and TNF-α which are proinflammatory mediators involved in tumorigenesis and progression of blood cancer. Additionally, evaluation of direct inhibitory effects on the growth of diverse blood cancers including leukemia, lymphoma, and myeloma cell lines unveiled compound 2v as the most potential molecules eliciting at least five-folds the potency of the standard imatinib drug over the used diverse blood cancers. Furthermore, compound 2v showed good selectivity to blood cancer cells rather than normal MRC5 cells. Moreover, compound 2v triggered death of HL60 leukemia cells via apoptosis induction. In conclusion, the natural product-derived compound 2v might serve as a multifunctional lead compound for further development of agents for treatment of blood cancers.

Synthesis and biological evaluation of anthracene-9,10 dione derivatives as CK2 inhibitors

Human protein kinase CK2 is an important target for the development of anticancer drugs. Many inhibitors were developed in the last few decades, among them emodin, a natural inhibitor with anthracene-9,10-dione backbone. In this work the inhibitory activity of another natural compound endocrocin having similar chemical structure to emodin was evaluated and turned out to be a moderate inhibitor with IC50 value of 6 µM. Additionally, a series of anthracene-9,10-dione derivatives was synthesized and their inhibitory activity toward the target enzyme was evaluated and compared to the activity of emodin. Only one compound namely 1-amino-6-methylanthracene-9,10-dione (4i) resulted be a potent inhibitor with an IC50 value of 1.45 µM. The rest of derivatives showed moderate or no inhibitory activities when were tested at 10 µM concentration. Additionally, the effect of emodin, endocrocin and compound 4i was evaluated on breast cancer cells (MCF7). Using IncuCyte TM life cell monitoring, cell growth of MCF7 cells was blocked almost completely after addition of 30 µM of emodin, whereas endocrocin was able to reduce cell growth by around 45%. Endocrocin with a concentration of 30 µM was able to reduce the viability of MCF7 cells to around 70% after 48 h of incubation. While only 20% of MCF7 cells were still able to synthesize DNA upon incubation with 100 μM endocrocin for 24 h. On the other hand, compound 4i showed weak effect on MCF7 cell line.

4-Thiazolidinone Based 5-Arylidene Hybrids: Design, Synthesis, Antimicrobial Activity, and Molecular Docking Studies

In recent years, the most pressing challenge in drug development has been the fight against bacterial drug resistance. Microbes have developed resistance against the present classes of antibiotics, necessitating the development of new antibiotics capable of replacing less effective drugs commercially accessible in the market. In order to achieve this, a straightforward technique for the synthesis of 4-thiazolidinone-based pyrazole-pyridine hybrids was designed (5a–o). The hybrids were characterized using spectroscopic techniques and tested for antimicrobial efficacy against a variety of bacterial and fungal species. The MIC value of compounds 5d, 5f, 5j, 5 l, 5 m, and 5o against tested bacterial strains was 62.5 μg/mL. Compound 5i showed a MIC value of 250 μg/mL against Candida albicans, which is twice the activity of the standard drug. Furthermore, to rationalize the antimicrobial finding and to gain an insight into the plausible mechanism of action, molecular docking study was performed against microbial DNA gyrase. A very significant correlation obtained between the in silico binding affinity and the antimicrobial activity could set an excellent platform for structure based drug design.

K2CO3-nanoparticles catalyzed the synthesis of 3-arylidine imidazo[1,2-c]pyrimidine candidates: Cytotoxic activity and docking study

The present work describes an green and eco-friendly synthetic protocol, and vitro anti-proliferative activity of a new series of 3-arylidine imidazo[1,2-c]pyrimidines. The target molecules 4a–p were synthesized via one-pot cyclization of 6-amino-4-(4-chlorophenyl)-2-thioxo-1,2-dihydropyrimidine-5-carbonitrile(1) with chloroacetyl chloride followed by condensation with a series of aromatic and heteroaromatic aldehydes in the presence of K2CO3-NPs at room temperature. The high yield (80–96%), mild reaction conditions (short reaction time and no heat needed), simple purification, and soft, cheap, high efficiency readily available and stability of K2CO3-NPs are evident features of the present approach. Pyrimidines 4c, 4 g and 4i demonstrated significant anti-proliferative activity against MCF-7 especially compound 4i was found to be the most effective among the tested compounds with IC50 values 3.83 µg/ml in MCF-7 cell line compared to the standard drug doxorubicin. In addition, compounds 4b, 4c, 4d, 4i, and 4n demonstrated high cytotoxic activity against HCT116, particularly compound (4b) was the most potent among the tested compounds with IC50 values 9.3 µg/ml in HCT116 cell line compared to doxorubicin.

Design, Synthesis, and Evaluation of the COX-2 Inhibitory Activities of New 1,3-Dihydro-2H-indolin-2-one Derivatives.

Thirty-three 1,3-dihydro-2H-indolin-2-one derivatives bearing α, β-unsaturated ketones were designed and synthesized via the Knoevenagel condensation reaction. The cytotoxicity, in vitro anti-inflammatory ability, and in vitro COX-2 inhibitory activity of all the compounds were evaluated. Compounds 4a, 4e, 4i-4j, and 9d exhibited weak cytotoxicity and different degrees of inhibition against NO production in LPS-stimulated RAW 264.7 cells. The IC50 values of compounds 4a, 4i, and 4j were 17.81 ± 1.86 μM, 20.41 ± 1.61 μM, and 16.31 ± 0.35 μM, respectively. Compounds 4e and 9d showed better anti-inflammatory activity with IC50 values of 13.51 ± 0.48 μM and 10.03 ± 0.27 μM, respectively, which were lower than those of the positive control ammonium pyrrolidinedithiocarbamate (PDTC). Compounds 4e, 9h, and 9i showed good COX-2 inhibitory activities with IC50 values of 2.35 ± 0.04 µM, 2.422 ± 0.10 µM and 3.34 ± 0.05 µM, respectively. Moreover, the possible mechanism by which COX-2 recognized 4e, 9h, and 9i was predicted by molecular docking. The results of this research suggested that compounds 4e, 9h, and 9i might be new anti-inflammatory lead compounds for further optimization and evaluation.

Synthesis and biological evaluation of coumarine-imidazo[1,2-c][1,2,3]triazoles: PEG-400 mediated one-pot reaction under ultrasonic irradiation

Synthetic chemists have organized easy and effective ways for perfect synthesis in response to the requirement for scaffolds that are crucial for medical applications. To investigate the synthesis of fused 1,2,3-triazoles in the presence and absence of ultrasound, the [3 + 2] cycloaddition followed by CN bond formation reaction between 3-(iodoethynyl)-2H-chromen-2-one and substituted 2-chloro-N-phenylacetamides was carried out under relatively optimized conditions. The cancer activity of the synthesized compounds were then tested in vitro against two MCF-7 and A-549 and the majority of the examined compounds 4e-4o showed significant activity, with compounds 4f, 4 g, and 4 h surpassing the standard drug against the A-549 line, and 4 m and 4n excelling it against MCF-7. Later, in vitro EGFR results revealed that compounds 4f (IC50 = 0.420 ± 0.08 μM), 4 g (IC50 = 0.367 ± 0.02 μM), and 4 h (IC50 = 0.453 ± 0.02 μM) were more effective than the conventional medicine Erlotinib (IC50 = 0.460±0.06 μM). In silico investigations of more potent compounds (4f, 4 g, 4 h, 4i, 4k, 4 m, and 4n) and erlotinib on the EGFR protein indicated that all seven compounds had much higher binding energies and inhibition constants than the erlotinib. Finally, the in silico pharmacokinetic profile of compounds 4f, 4 g, 4 h, 4i, 4k, 4 m, and 4n was estimated using SWISS/ADME and pkCSM, where all compounds followed Lipinski, Veber, Egan, and Muegge rules without deviation.

Eu-Gd@BiPO4 nano-composite: A potential heterogeneous catalyst in Biginelli reaction

The Biginelli reaction found a prominent place among multicomponent reactions owing to the widespread pharmacological importance of the products dihydropyrimidinones (DHPMs). In the present work, DHPM analogs of Vanillin have been synthesized in a one-step Biginelli condensation of Vanillin, 1,3-diketo compound and urea in the presence of 5 mol% of the Eu-Gd@BiPO4 nano-composite catalyst. The heterogeneous catalyst afforded the desired DHPM products of Vanillin in high to excellent yields (85–93%) in a short interval of 30 mins at 80 °C under solvent less conditions. Being heterogeneous, the nano-composite catalyst was easily recovered after the reaction and re-employed in the Biginelli synthesis 5 times without any treatment or significant activity loss. The synthesized DHPM analogs of Vanillin were screened for their antioxidant and antibacterial potential. Out of nine compounds, three compounds 4e, 4h, and 4i were found to show the maximum %RSA of 66.7, 67, and 71% respectively in the DPPH assay and reducing power assay analysis respectively, in comparison to %RSA of 80.9 by the standard Ascorbic acid. The compounds 4a, 4d & 4e were able to inhibit the growth of both gram-positive and gram-negative bacteria to a considerable extent as predicted by the disc diffusion method.

In silico and in vitro studies of novel cyanoacrylamides incorporating pyrazole moiety against breast and prostate carcinomas

We report novel cyanoacrylamide derivatives bearing the pyrazole moiety. The molecular structures of the prepared cyanoacrylamides were confirmed by the different spectral tools such as NMR, IR, and elemental analyses. The anticancer effect of all the newly prepared cyanoacrylamides was studied against four cancer cell lines (HEPG2, MCF7, PACA2, and PC3) as well as the normal cell line (BJ1). The best cytotoxic effect was shown against PC3, where compounds 5f and 5i revealed promising IC50 values (11.7 and 66.8 µM) respectively compared to doxorubicin (43.8 µM). In addition, the effective compounds were screened against a normal BJ1 cell line, which showed promising selectivity against PC3 and moderate selectivity toward MCF7 cells. The molecular docking study showed the affinities of compounds 5c and 5d toward STAT1 protein and compound 5i toward KRAS with promising energy scores. The subsequent molecular experiments were studied on compounds 5b, 5c, 5d, 5f, and 5i. Quantitative Real-time-PCR revealed that the expression of RBL2 and STAT2 genes were down-regulated in 5c and 5d treated MCF7 cells much lower than the other treated MCF7 samples. Also, the expression level of KRAS and SMAD genes was determined, which revealed the significant down-regulation of them in compounds 5f and 5i treated PC3 cells. The percentages of DNA damage were raised significantly in all treated MCF7 and PC3 samples as compared to the negative control, and the highest percentages were for compounds 5c and 5d treated MCF7 cells.Graphical

Synthesis, in silico and in vitro studies of hydrazide-hydrazone imine derivatives as potential cholinesterase inhibitors.

A series of hydrazide-hydrazone imine derivative compounds (3a-k) were synthesized and their structures characterized using FTIR, 1 H, and 13 C (NMR) spectroscopic methods. In addition, molecular structures of compounds 3a, 3d, and 3g were elucidated by X-ray diffraction technique. In vitro inhibition activities of hydrazide-hydrazone imine derivatives against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) were investigated. Compound 3i (IC50 = 2.01 μM) exhibited the best inhibitory activity against AChE, comparable to the control Galantamine (IC50 = 2.60 μM). Against BChE, compound 3h (IC50 = 2.83 μM) showed the best inhibitory property which is higher control Galantamine (IC50 = 3.70 μM). The Ki values of compound 3i (Ki = 0.63 μM) and compound 3h (Ki = 0.94 μM) that have the strongest inhibitory potential were determined against AChE and BChE, respectively. According to the docking result, the most stable conformation of AChE and compound 3i showed that it has a binding affinity of -10.82 kcal/moL. The binding affinity of the most stable conformation formed by BChE and compound 3h is -8.60 kcal/moL. Finally, in silico results and pharmacokinetic parameters of ADME showed that these compounds have good oral bioavailability properties.

Synthesis, biological evaluation and molecular modeling studies of modulated benzyloxychalcones as potential acetylcholinesterase inhibitors

Acetylcholinesterase inhibitors (AChEIs) have become a significant target in the search for an efficient treatment of Alzheimer’s disease. Chalcone-based compounds display a strong potency to hinder AChE. So, this study focused on the synthesis of a series of new chalcone derivatives with anti-cholinesterase potential and their structures were characterized based on spectroscopic methods including IR, 1H NMR, 13C NMR and HRMS. Chalcone derivatives were screened against AChE. Most of them exhibited potent inhibitory activity against AChE. Compound 11i showed the most potent activity toward acetylcholinesterase compared to the positive compound, Galantamine. Docking studies into the active site of the acetylcholinesterase enzyme ravealed the significant docking score of the synthesized compounds with docking score of −7.959 to −9.277 kcal/mol when compared to the co-crystallized ligand, Donepezil (−10.567 kcal/mol). The interaction’s stability was further assessed using a conventional atomistic 100 ns dynamics simulation study, which revealed the conformational stability of representative compound 11i in the cavity of the acetylcholinesterase enzyme. Communicated by Ramaswamy H. Sarma

Design, synthesis of benzimidazole tethered 3,4-dihydro-2H-benzo[e] [1, 3] oxazines as anticancer agents.

A series of novel 3-(1H-benzo[d]imidazol-2-yl)-3,4-dihydro-2H-benzo[e][1,3] oxazine analogues synthesized through a two-step synthetic protocol. The structure of the compounds were established by interpretation 1H NMR, 13C NMR and Mass spectral data recorded after purification. All the title compounds 4a-k were screened for their in vitro anti-cancer activity against two breast cancer cell lines MCF 7 and MDA-MB-231 by using Doxorubicin as standard reference. Compound 4e displayed superior activity against both the cell lines MCF-7 and MDA-MB-231 with IC50 values of 8.60 ± 0.75 and 6.30 ± 0.54µM respectively, compared to the Doxorubicin IC50 value of 9.11 ± 0.54 and 8.47 ± 0.47µM. Compound 4i also indicated good activity with IC50 value of 9.85 ± 0.69μM on par with Doxorubicin against MCF-7 cells. Compound 4g demonstrated best activity on par with standard reference to IC50 value of 8.52 ± 0.62μM against MDA-MB-231 cell line. And all other compounds demonstrated good to moderate activity compared to Doxorubicin. Docking studies against EGFR showed that all the compounds have very good binding affinities towards the target. The predicted drug-likeness properties of all compounds enable them to be used as therapeutic agents.

Design, Synthesis, and Evaluation of a New Series of Hydrazones as Small-Molecule Akt Inhibitors for NSCLC Therapy.

In an endeavor to identify small molecules for the management of non-small-cell lung carcinoma, 10 new hydrazone derivatives (3a-j) were synthesized. MTT test was conducted to examine their cytotoxic activities against human lung adenocarcinoma (A549) and mouse embryonic fibroblast (L929) cells. Compounds 3a, 3e, 3g, and 3i were determined as selective antitumor agents on A549 cell line. Further studies were conducted to figure out their mode of action. Compounds 3a and 3g markedly induced apoptosis in A549 cells. However, both compounds did not show any significant inhibitory effect on Akt. On the other hand, in vitro experiments suggest that compounds 3e and 3i are potential anti-NSCLC agents acting through Akt inhibition. Furthermore, molecular docking studies revealed a unique binding mode for compound 3i (the strongest Akt inhibitor in this series), which interacts with both hinge region and acidic pocket of Akt2. However, it is understood that compounds 3a and 3g exert their cytotoxic and apoptotic effects on A549 cells via different pathway(s).

Synthesis, antimicrobial activity, electrochemical studies and molecular modeling studies of novel 1,3,4-oxadiazole derivatives

The high incidence of antimicrobial-resistant (AMR) infections in recent decades has made the development of novel antimicrobial medications one of the medicinal chemists' top priorities. In this study, synthesis, in vitro antimicrobial activity, electrochemical studies, in silico pharmacokinetic ADME parameters, molecular docking, and molecular dynamic simulations were all performed on several 1,3,4-oxadiazole derivatives. The minimum inhibitory concentrations (MIC) of these compounds were evaluated against eleven species of gram-positive bacteria, gram-negative bacteria and fungal pathogens using azithromycin as the reference antibacterial agent, voriconazole and fluconazole as the reference antifungal agents. Both compounds 4d and 4f were found to be approximately as effective as azithromycin against E. faecalis and E. coli, respectively while three compounds showed antifungal activity against C. parapsilopsis, with MIC values that were identical to fluconazole for 4g and 4i, and to voriconazole for 4j. Also, the most potent derivatives-double stranded DNA (dsDNA) interactions were evaluated using an electrochemical technique. Compounds 4d, 4f and 4i were found to disrupt the structure of dsDNA however compound 4h wasn't able to bind to dsDNA. In addition, the structure-activity relationship (SAR) of compounds 4f and 4d were elucidated by molecular modeling studies.

Design, Synthesis and Biological Evaluation of Novel Catalpol Derivatives as Potential Pancreatic Cancer Inhibitors.

A series of C10-position imidazole-modified catalpol derivatives are specifically designed and synthesized for serving as potential pancreatic cancer inhibitors, which are characterized by 1 H NMR, 13 C NMR and high-resolution mass spectrometry (HRMS). They were evaluated by the 3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide (MTT) test on two human pancreatic cancer cells PANC-1, BxPC-3 and normal pancreatic cell HPDE6-C7, which showed the significant inhibitory effected on the growth of human pancreatic cancer cells of PANC-1 and BxPC-3, especially 91.6% efficacy on BxPC-3, and 73.1% on PANC-1. Simulation studies like molecular docking supported strong binding of vascular endothelial growth factor receptor 2 (VEGFR-2) protein tyrosine kinase (PDB ID: 4AGD), a target of pancreatic cancer. A novel imidazol-modified catalpol compound 3i with strong inhibitory effect on pancreatic cancer cells, which could potentially develop into anti-pancreatic cancer drug candidates in the future.

Synthesis and Anti-Tubercular Screening of 8-Benzyloxy-5-[2-(Substituted-Phenyl)-Thiazol-4-yl]-1H-Quinolin-2-One Derivatives

Novel 8-Benzyloxy-5-[2-(substituted-phenyl)-thiazol-4-yl]-1H-quinolin-2-one derivatives are synthesized by the cyclocondensation of substituted thiobenzamide and in-situ generated 8-benzyloxy-5-(2-bromo-acetyl)-1H-quinolin-2-one in the ethanol using simple one-pot multicomponent protocol under catalyst-free reaction conditions. All the products were screened for anti-tuberculosis (TB) activity against Mycobacterium tuberculosis H37Rv stains using L. J. medium conventional method and Compound 4h show good and Compound 4a, 4c, 4e, 4g, 4i, and 4j are also showing significant activity against M. tuberculosis.

Discovery of novel N-aryl-2-trifluoromethyl-quinazoline-4-amine derivatives as the inhibitors of tubulin polymerization in leukemia cells

A series of new N-aryl-2-trifluoromethylquinazoline-4-amine analogs were designed and synthesized based on structure optimization of quinazoline by introducing a trifluoromethyl group into 2-position. The structures of the twenty-four newly synthesized compounds were confirmed by 1H NMR, 13C NMR and ESI-MS. The in vitro anti-cancer activity against chronic myeloid leukemia cells (K562), erythroleukemia cells (HEL), human prostate cancer cells (LNCaP), and cervical cancer cells (HeLa) of the target compounds was evaluated. Among them, compounds 15d, 15f, 15h, and 15i showed the significantly (P < 0.01) stronger growth inhibitory activity on K562 than those of the positive controls of paclitaxel and colchicine, while compounds 15a, 15d, 15e, and 15h displayed significantly stronger growth inhibitory activity on HEL than those of the positive controls. However, all the target compounds exhibited weaker growth inhibition activity against K562 and HeLa than those of the positive controls. The selectivity ratio of compounds 15h, 15d, and 15i were significantly higher than those of other active compounds, indicating that these three compounds had the lower hepatotoxicity. Several compounds displayed strong inhibition against leukemia cells. They inhibited tubulin polymerization, disrupted cellular microtubule networks by targeting the colchicine site, and promoted cell cycle arrest of leukemia cells at G2/M phase and cell apoptosis, as well as inhibiting angiogenesis. In summary, our research provided that novel synthesized N-aryl-2-trifluoromethyl-quinazoline-4-amine active derivatives as the inhibitors of tubulin polymerization in leukemia cells, which might be a valuable lead compounds for anti-leukemia agents.

In Silico Design of New Dual Inhibitors of SARS-CoV-2 MPRO through Ligand- and Structure-Based Methods.

The viral main protease is one of the most attractive targets among all key enzymes involved in the life cycle of SARS-CoV-2. Considering its mechanism of action, both the catalytic and dimerization regions could represent crucial sites for modulating its activity. Dual-binding the SARS-CoV-2 main protease inhibitors could arrest the replication process of the virus by simultaneously preventing dimerization and proteolytic activity. To this aim, in the present work, we identified two series' of small molecules with a significant affinity for SARS-CoV-2 MPRO, by a hybrid virtual screening protocol, combining ligand- and structure-based approaches with multivariate statistical analysis. The Biotarget Predictor Tool was used to filter a large in-house structural database and select a set of benzo[b]thiophene and benzo[b]furan derivatives. ADME properties were investigated, and induced fit docking studies were performed to confirm the DRUDIT prediction. Principal component analysis and docking protocol at the SARS-CoV-2 MPRO dimerization site enable the identification of compounds 1b,c,i,l and 2i,l as promising drug molecules, showing favorable dual binding site affinity on SARS-CoV-2 MPRO.

Design, synthesis, and docking of novel thiazolidine-2,4-dione multitarget scaffold as new approach for cancer treatment.

Novel thiazolidine-2,4-diones have been developed and estimated as conjoint inhibitors of EGFRT790M and VEGFR-2 against HCT-116, MCF-7, A549, and HepG2 cells. Compounds 6a, 6b, and 6c were known to be the dominant advantageous congeners against HCT116 (IC50 = 15.22, 8.65, and 8.80 µM), A549 (IC50 = 7.10, 6.55, and 8.11 µM), MCF-7 (IC50 = 14.56, 6.65, and 7.09 µM) and HepG2 (IC50 = 11.90, 5.35, and 5.60 µM) mass cell lines, correspondingly. Although compounds 6a, 6b, and 6c disclosed poorer effects than sorafenib (IC50 = 4.00, 4.04, 5.58, and 5.05 µM) against the tested cell sets, congeners 6b and 6c demonstrated higher actions than erlotinib (IC50 = 7.73, 5.49, 8.20, and 13.91 µM) against HCT116, MCF-7 and HepG2 cells, yet lesser performance on A549 cells. The hugely effective derivatives 4e-i and 6a-c were inspected versus VERO normal cell strains. Compounds 6b, 6c, 6a, and 4i were found to be the most effective derivatives, which suppressed VEGFR-2 by IC50 = 0.85, 0.90, 1.50, and 1.80 µM, respectively. Moreover, compounds 6b, 6a, 6c, and 6i could interfere with the EGFRT790M performing strongest effects with IC50 = 0.30, 0.35, 0.50, and 1.00 µM, respectively. What is more, 6a, 6b, and 6c represented satisfactory in silico computed ADMET profile.

Novel Benzimidazol‐2‐Thione Derivatives: Synthesis, In Vitro Anticancer, Antimicrobial Activities, And In Silico Molecular Docking Study

AbstractA series of derivative benzimidazol‐2‐thione compounds (2 a–2 l) had been synthesized, screened for their antimicrobial activities by dish diffusion and dilution assays, anti‐tumor against breast, rhabdomyosarcoma, and liver human cancer cell lines via MTT assay, followed by carrying out in silico docking model. Entries 2 i–2 j, 2 l, and 2 g are novel compounds, among them, compound 2i manifested the highest antibacterial activity against both Methicillin‐resistant Staphylococcus aureus and Streptococcus faecalis; meanwhile, entries 2 i–2 j and 2 l showed significant antifungal activity toward Trichophyton mentagrophytes, Trichophyton rubrum, and Microsporum gypseum. Through in vitro approach, entry 2 i is the best derivative against human rhabdomyosarcoma cell line. Additionally, via in silico approach, entry 2 i reasonably explained drug delivery ligand against bacterium Streptococcus faecalis, moreover, entries 2 i–2 j and 2 l showed excellent antifungal activity, explained via enzyme inhibition mechanism against 2VF5. In silico, 2 i was proved to inhibit against sarcoma cancer cell line.