Final Compounds Research Articles

Design, synthesis, and biological evaluation of novel quinoxaline aryl ethers as anticancer agents.

We designed and synthesized thirty novel quinoxaline aryl ethers as anticancer agents, and the structures of final compounds were confirmed with various analytical techniques like Mass, 1 H NMR, 13 C NMR, FTIR, and elemental analyses. The compounds were tested against three cancer cell lines: colon cancer (HCT-116), breast cancer (MDA-MB-231), prostate cancer (DU-145), and one normal cell line: human embryonic kidney cell line (HEK-293). The obtained results indicate that two compounds, FQ and MQ, with IC50 values < 16 μM, were the most active compounds. Molecular docking studies revealed the binding of FQ and MQ molecules in the active site of the c-Met kinase (PDB ID: 3F66, 1.40 Å). Furthermore, QikProp ADME prediction and the MDS analysis preserved those critical docking data of both compounds, FQ and MQ. Western blotting was used to confirm the impact of the compounds FQ and MQ on the inhibition of the c-Met kinase receptor. The apoptosis assays were performed to investigate the mechanism of cell death for the most active compounds, FQ and MQ. The Annexin V/7-AAD assay indicated apoptosis in MDA-MB-231 cells treated with FQ and MQ, with FQ (21.4%) showing a higher efficacy in killing MDA-MB-231 cells than MQ (14.25%). The Caspase 3/7 7-AAD assay further supported these findings, revealing higher percentages of apoptotic cells for FQ-treated MDA-MB-231 cells (41.8%). The results obtained from the apoptosis assay conclude that FQ exhibits better anticancer activity against MDA-MB-231 cells than MQ.

Design, Synthesis, and Biological Effect Studies of Novel Benzofuran-Thiazolylhydrazone Derivatives as Monoamine Oxidase Inhibitors.

In recent studies, monoamine oxidase (MAO) inhibitory effects of various thiazolylhydrazone derivatives have been demonstrated. Within the scope of this study, 12 new compounds containing thiazolylhydrazone groups were synthesized. The structures of the obtained compounds were elucidated by 1H NMR, 13C NMR, and high-resolution mass spectrometry (HRMS) methods. The inhibitory effects of the final compounds on MAO enzymes were investigated by means of in vitro methods. In addition to enzyme inhibition studies, enzyme kinetic studies of compounds with high inhibitory activity were examined, and their effects on substrate-enzyme relations were investigated. Additionaly, cytotoxicity tests were carried out to determine the toxicities of the selected compounds, and the compounds were found to be nontoxic. The interactions of the active compound with the active site of the enzyme were characterized by in silico methods.

Deciphering the intriguing molecular recognition of a novel indene-phloroglucinol tethered compound with human serum albumin using multi-spectroscopy and molecular docking studies

A new indene-phloroglucinol tethered compound IPC1 was synthesized in our laboratory in three steps. The interaction of the final compound IPC1 with human serum albumin (HSA) was studied using multi-spectroscopic and molecular docking methods. UV–vis and fluorescence studies confirmed the spontaneous formation of ground state complex and the values of the binding constants were found to be in the order of 104 M−1 (4.727×104 M−1 at 290.15 K). Positive ΔS° (+112.797 J K−1 mol−1) and ΔH° (+6.756 KJ mol−1) indicate the involvement of hydrophobic interaction as the major contributing force in the complex formation process. Site marker studies suggested that the compound IPC1 binds near the subdomain IIIA of HSA, which was further supported by fluorescence spectroscopic and molecular docking analysis.

Novel oxadiazole functionalized pyridopyrimidine derivatives; their anticancer activity and molecular docking studies

AbstractA series of novel oxadiazole functionalized pyridopyrimidine derivatives prepared starting from 6‐methyl/ethyl‐2‐oxo‐4‐(trifluoromethyl)‐1,2‐dihydropyridine‐3‐carbonitrile 1. This compound 1 on reaction with sulfuric acid obtained compound 2, further compound 2 on reaction with chloroacetamide followed by reaction with ethoxy methylene malonic diethyl ester coupling and further cyclization to obtain compound 5. Compound 5 on reaction with hydrazide hydrate obtained hydrazide derivatives 6. Compound 6 on reaction with diverse substituted aromatic acids to get oxadiazole derivatives 7a–l. All the final compounds 7a–l evaluated for anticancer 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); and MCF7—breast cancer (HTB‐22) and promising compounds 7d and 7k have been identified and evaluated for molecular docking interactions.

Synthesis and Anti-bacterial Activity Evaluation against Mycobacterium tuberculosis of New Quinoline Derivatives Coupled with the Camphor Nucleus

Abstract: Tuberculosis is a serious infectious disease caused by Mycobacterium tuberculosis (Mtb), also known as Koch’s bacillus. The involvement of latent forms and resistant strains has aggravated the situation, making the disease a serious public health problem. : The objective of the study was to synthesize and evaluate ten new compounds containing camphor nucleus coupled to quinolinic derivatives as probable inhibitors of sensitive and resistant strains of Mtb growth. : The synthesis of the final compounds, 3a-e and 4a-e, was based on the use of intermediates previously obtained, in which the coupling of the camphor nucleus to quinoline derivatives was carried out via a convergent route, which resulted in good yields (50-80%). All the final compounds were fully characterized, and the 3-dimensional molecular structure of compound 4c was determined. The antimycobacterial activities of all compounds against Mtb strains were evaluated and the cytotoxicity test was conducted using the in vitro microplate procedure with broth microdilution assay (MTT). : Compound 3e was the most active against sensitive and resistant strains, with a minimal inhibitory concentration (MIC) of 9.5 μM similar to ethambutol, a first-line drug used against the tuberculosis. The most active compound 3e was selected for the potential activity against Vero cells and it displayed no cytotoxicity at a concentration near the MIC value. : The final compounds were obtained in good yields, with derivative 3e being the most promising with high activity and low cytotoxicity. Such findings open new perspectives for drug development based on the incorporation of camphor nucleus in selected compounds.

Synthesis of Novel Artemisinin, Ciprofloxacin, and Norfloxacin Hybrids with Potent Antiplasmodial Activity.

The synthesis and antiplasmodial evaluation of new hybrids combining the pharmacophore structures of artemisinin, ciprofloxacin or norfloxacin, and 7-chloroquinoline are reported in this study. The first step for all of the syntheses is the obtainment of key piperazine esters intermediates bearing the drugs ciprofloxacin and norfloxacin. Using these platforms, 18 final compounds were synthesized through a multistep procedure with overall yields ranging between 8 and 20%. All compounds were screened for their antiplasmodial activity against the chloroquine-resistant Plasmodium falciparum FcB1 strain. Compounds 20, 21, 22, and 28, bearing an artesunate fragment with ciprofloxacin, exhibited IC50 values in the range of 3.5-5.4 nM and excellent selectivity indices. Among the compounds bearing the artesunate moiety on the norfloxacin, two of them, 23 and 24, afforded IC50 values of 1.5 nM and 1.9 nM, respectively. They also showed excellent selectivity indices. The most potent compounds were also evaluated against the CQ-resistant Dd2 strain of Plasmodium falciparum, demonstrating that those compounds incorporating the artesunate fragment were the most potent. Finally, the combination of artesunate with either ciprofloxacin or norfloxacin moieties in a single molecular entity proved to substantially enhance the activity and selectivity when compared to the administration of the unconjugated counterparts artesunate/ciprofloxacin and artesunate/norfloxacin.

Mechanical Alloying Synthesis of AB3 Zirconium Substituted Intermetallic

Abstract: Several ternary RareEarth-Magnesium-Nickel intermetallics (RE-Mg-Ni) emerged in last decade for their specific hydrogen storage capability. Nickel is now considered among strategic metals with recurrent rising price, Magnesium although its good gravimetric facility suffers from frequent oxidation or irreversible poisoning. Zirconium alloys are recognized for their improved anti-corrosion properties with enhanced wear resistance for high temperature machinability in industrial applications or energy research purposes. We proposed in this paper double substitution possibility replacing Magnesium and reducing Nickel charge. We developed new generation of quaternary Zirconium-AB3 intermetallic LaZr2Ni5Al4 using mechanical alloying method. Two binary raw materials are involved in this alloying reaction, the first is LaNi5 and the second is ZrAl2 (Laves phase C14) and both precursors are achieved quasi-quantitively using high frequency induction melting. The final target AB3 compound crystallizes in Trigonal system with space group R-3m (166) and following experimental conditions (Fritsch P7, Ω = 450 rpm) an acceptable synthesis yield (&amp;gt;80%) is obtained starting from 20 hours mechanical alloying. Rietveld refinement is performed to have real matrix parameters and AB3 powder surface is analyzed using Scanning Electron Microscopy.

Design, Synthesis, in vitro Anti‐inflammatory Activity and in silico Studies of Imidazole‐Based 1,2,3‐Triazole Hybrids Targeting p38 MAP Kinase

Abstractp38 MAP kinases are involved in numerous inflammatory diseases. A series of 14 molecules of 1,2,3 triazole linked 4‐((2‐cyclohexyl‐4,5‐diphenyl‐1H‐imidazol‐1‐yl) methyl)‐1‐phenyl hybrids(7 a–7 n) has been synthesized by click reaction. Spectral data characterized all the synthesized compounds. The final compounds were screened for in vitro p38 MAP kinase inhibitory activity. Three compounds from the series 7 c, 7 f, and 7 n expounded superior activity with IC50 values 234.08±19.65 nM, 222.68±20.69 nM, and 241.70±20.51 nM respectively while two compounds (7 d and 7 e) showed considerable activity compared to prototype drug Adezmapimod (SB203580) (IC50 value 257.13±23.94 nM). The docking study of synthesized molecules revealed that the three compounds (7 f,7 g, and 7 n) showed higher binding affinities than Adezmapimod. The “Desmond v3.6 Program” was utilized to conduct MD simulations. The result revealed that compound 7 f was conformationally stable. The ADME studies were performed using the Swiss ADME algorithm. Studies revealed that all the compound‘s defiance of Lipinski's rule is within acceptable ranges with few violations. Compound 7 f was orally active and showed good gastrointestinal absorption within the acceptable range. The search for newer compounds with increased activity compared to Adezmapimod resulted in identifying a novel subclass of p38 MAP kinase inhibitors.

Synthesis, Corrosion Inhibition Efficiency in Acidic Media, and Quantum Chemical Studies of Some Hydrazine Derivatives

In this work, four hydrazone Schiff base derivatives N-(2,4-Dinitro-phenyl)-N’-(1H-pyrrol-2-ylmethylene)-hydrazine (1a), N-Benzo [1,3] dioxol-5-ylmethylene-N’-(2,4-dinitro-phenyl)-hydrazine (1b), (E)-5-((2-(2,4-dinitrophenyl)hydrazono)methyl)-2-hydroxybenzoic acid (1c) and (E)-1-(2,4-dinitrophenyl)-2-(2-methoxybenzylidene)hydrazine (1d) were synthesized by reaction of four aldehydes namely pyrrole-2-carboxaldehyde, piperonal, 5-formylsalicylic acid, and o-vanillin with 2,4-dinitrophenyl hydrazine to produce the final compounds 1a, 1b, 1c, and 1d, respectively. These four compounds were investigated as corrosion inhibitors in aqueous mild acidic static solution. FTIR, HNMR, and elemental analysis were used to elucidate the chemical structure of the synthesized inhibitors. Using potential dynamic polarization measurements, these inhibitors’ efficiency in preventing C-steel corrosion in 1.00 M HCl was studied. The results of the experiments revealed that 1×10−3 M is the ideal concentration for 1a, 1b, 1c, and 1d, and that the corresponding inhibition efficiencies for these subunits were 80.70%, 91.30%, 91.34, and 88.80%, respectively. The best corrosion inhibitors were compounds 1b and 1c. Furthermore, studies suggested that these substances are mixed-type inhibitors and that the efficiency of the inhibition is strongly correlated with their quantity. Quantum paraments included Dipole moment, energy band gap (ΔE), value of energy of lowermost unoccupied molecular orbital (ELUMO), and energy of high most occupied molecular orbital (EHOMO) using Molecular Operating Environment MOE, Gaussian, and HyperChem software packages were determined which demonstrated strong agreement between algorithmic and practical findings.

Design and characterization of iron–calcium–aluminium–silicate–hydrate as low-temperature binder

This work aims to synthesize new cementitious materials (binders) using marble powder, rice husk ash, activated laterite and NaOH solution by applying low energy process. The binder was used to stabilize solid precursors (laterite and pozzolan). To achieve this objective, calcium–silicate–hydrate (CSH) was first synthesized at different temperatures (26, 50, 80 and 100 °C). The best physical–mechanical properties were chosen to produce iron–calcium–aluminium–silicate–hydrate [Fe–C(A)SH] at different concentrations of sodium hydroxide solution: 4, 5, 6 M. Finally, the formulated binder at 6 M of NaOH solution was used to stabilize laterite and pozzolans at the following proportions 20%, 30%, 40% and 50%. The samples were characterized after 28 days of curing at room temperature. FT-infrared spectroscopy, X-ray diffraction, and environmental scanning electron microscope ESEM-EDS permitted to confirm the formation of CSH, and Fe–C(A)SH. The mechanical test used to evaluate the performance showed that the incorporation of 10% iron-rich laterite into CSH increased the strength up to 42.93 MPa and the addition of Fe–C(A)SH in the laterite/pozzolans increased the compressive strength of the final product (15.34 and 15.8 MPa for laterite and pozzolan, respectively). The highest concentration (6 M) increases the alkalinity and reduces the efficiency of silicate polymerization affecting the final structural compound. From the results, low-energy Fe–C(A)SH-based cement and stabilized compounds appeared promising for the development of sustainable infrastructures.

Statistical-physical method for simulating the transport of microplastic-antibiotic compound pollutants in typical bay area

Microplastics and antibiotics are emerging pollutants in the environment and have received widespread attention globally. In coastal areas, microplastic and antibiotic pollution is ubiquitous and often overlapping. Microplastic-antibiotic compound pollutants that are formed through adsorption have thus become a major concern. However, modeling knowledge of microplastic transport in coastal areas is still limited, and research on the impact of compound pollutants caused by Polythene (PE)-antibiotics in such settings is in early stages. In this study, using a lattice Boltzmann method (LBM) and temporal Markov method (TMM) under a statistical-physical framework, we simulated pollutant transport and PE-antibiotic compound pollutants in coastal areas. First, a series of models are proposed, including an LBM wave-current coupling model, an LBM antibiotic transport model, an LBM particle-tracking model, a TMM microplastic transport model and the final LBM-TMM hybrid compound pollutant model. Then, the suitability and applicability of the models was validated using experimental data and numerical simulations. Finally, the models were applied to a study area, Laizhou Bay (China). The simulation results demonstrate that adsorption will reduce the concentration of antibiotics in the water environment. Within 44 days, the adsorbed antibiotic carried by PE particles migrate further, and the width of the pollution zone escalates from 234.2 m to 689.0 m.

Application of a Deep Eutectic Solvent for the Synthesis of Novel Imidazole-Containing Quinazoline Derivatives as Potent Cytotoxic Agents

Background: Drugs containing the 4-anilinoquinazolines scaffold play a critical role in cancer treatment by inhibiting protein kinases, especially tyrosine kinases. In this study, a novel series of 4-anilinoquinazoline derivatives were synthesized and evaluated as cytotoxic agents. Methods: All final compounds were synthesized using two methods, including a conventional approach using potassium iodide and dimethylformamide as well as a green method using a deep eutectic solvent (DES) comprising choline chloride: urea. The cytotoxicity was tested on the A431, HUVEC, and HU02 cell lines. To evaluate the binding pattern of the compounds with EGFR and VEGFR-2, a molecular docking investigation was performed. Finally, the wound healing assay was carried out to assess the potency of compounds in inhibiting cell migration. Results: The final reaction time was approximately 15-20 min with yields of 60-72% using DES, while the conventional method took 3 to 4 h to complete, with yields between 30% and 42%. Compounds 8k and 8l showed better cytotoxicity against both cell lines compared to vandetanib (IC50=0.11 µM and 0.26 µM on A431 and IC50=5.01 µM and 5.24 µM on HUVEC, respectively). Molecular docking studies revealed that compound 8k, which contained 3-methylaniline at the 4-position of the quinazoline core, showed efficient binding affinity to both EGFR and VEGFR-2. An essential hydrogen bond was formed between quinazoline N1 of 8k and the Met796 residue of EGFR with a docking score of -8.76 kcal/mol. The imidazole N3 of 8k interacted with the Cyc919 residue of VEGFR-2, forming a hydrogen bond with a docking score of -9.03 kcal/mol. Moreover, compound 8k exhibited the best inhibitory activity on cell migration and wound healing. Conclusion: DES significantly improved the time and yield of the final reactions. Compound 8k, which showed the best cytotoxicity and inhibitory activity on cell migration, could be a suitable candidate for further structural optimization.

Synthesis, Molecular Docking, Characterization, and Preliminary Evaluation of Some New 1, 3-Diazetidin-2-One Derivatives as Anticancer Agents

A series of novel 1,3-diazetidin-2-one derivatives were designed, synthesized, and evaluated preliminary (In Vitro) for their cytotoxic activity against the lung (A549) cancer cell line. GOLD software (version 2021.2.0) was used to conduct a molecular docking study; the tested derivatives demonstrated significant anticancer activity compared to the reference drug (erlotinib). PLP-fitness values for the final compounds are 79.81, 80.80, and 81.57, respectively, whereas the reference ligand, erlotinib, had a value of 76.20. The synthesized compounds were identified and characterized using physicochemical parameters (melting points and Rf values), FTIR, 1H-NMR, and 13C-NMR spectroscopy. According to the IC50 values for the synthesized derivatives, compounds N4a and N4b exhibit outstanding anti-proliferative activity with IC50 value of (7.51, 7.68) µM against A549 cell line, compared to erlotinib, which has an IC50 value of (11.5) µM.

Comparative Effectiveness and Safety of Biologic Treatments in Giant Cell Arteritis: A Network Meta-analysis of Randomized Controlled Trials

Background: Drugs containing the 4-anilinoquinazolines scaffold play a critical role in cancer treatment by inhibiting protein kinases, especially tyrosine kinases. In this study, a novel series of 4-anilinoquinazoline derivatives were synthesized and evaluated as cytotoxic agents. Methods: All final compounds were synthesized using two methods, including a conventional approach using potassium iodide and dimethylformamide as well as a green method using a deep eutectic solvent (DES) comprising choline chloride:urea. The cytotoxicity was tested on the A431, HUVEC, and HU02 cell lines. To evaluate the binding pattern of the compounds with EGFR and VEGFR-2, a molecular docking investigation was performed. Finally, the wound healing assay was carried out to assess the potency of compounds in inhibiting cell migration. Results: The final reaction time was approximately 15-20 min with yields of 60-72% using DES, while the conventional method took 3 to 4 h to complete, with yields between 30% and 42%. Compounds 8k and 8l showed better cytotoxicity against both cell lines compared to vandetanib (IC50=0.11 µM and 0.26 µM on A431 and IC50=5.01 µM and 5.24 µM on HUVEC, respectively). Molecular docking studies revealed that compound 8k, which contained 3-methylaniline at the 4-position of the quinazoline core, showed efficient binding affinity to both EGFR and VEGFR-2. An essential hydrogen bond was formed between quinazoline N1 of 8k and the Met796 residue of EGFR with a docking score of -8.76 kcal/mol. The imidazole N3 of 8k interacted with the Cyc919 residue of VEGFR-2, forming a hydrogen bond with a docking score of -9.03 kcal/mol. Moreover, compound 8k exhibited the best inhibitory activity on cell migration and wound healing. Conclusion: Tocilizumab may be the most efficient remission-inducing and relapse-lowering biological agent for patients with GCA, and TNF inhibitors pose the highest risk of infection among the biologics studied.

Phosphine Catalyzed Michael-Type Additions: The Synthesis of Glutamic Acid Derivatives from Arylidene-α-amino Esters.

The reaction of arylidene-α-amino esters with electrophilic alkenes to yield Michael-type addition compounds is optimized using several phosphines as organocatalysts. The transformation is very complicated due to the generation of several final compounds, including those derived from the 1,3-dipolar cycloadditions. For this reason, the selection of the reaction conditions is a very complex task and the slow addition of the acrylic system is very important to complete the process. The study of the variation in the structural components of the starting imino ester is performed as well as the expansion of other electron-poor alkenes. The crude products have a purity higher than 90% in most cases without any purification. A plausible mechanism is detailed based on the bibliography and the experimental results. The synthesis of pyroglutamate entities, after the reduction of the imino group and cyclization, is performed in high yields. In addition, the hydrolysis of the imino group, under acidic media, represents a direct access to glutamate surrogates.

GREEN SYNTHESIS AND ANTIMICROBIAL EVALUATION OF SOME THIOSEMICARBAZONE AND SEMICARBAZONE DERIVATIVES

The interaction of substituted pyridine carboxaldehyde with thiosemicarbazide and semicarbazide via a greener approach resulted in the synthesis of thiosemicarbazone and semicarbazone derivatives; respectively. The resultant compounds were synthesized in aqueous media and were characterized by FTIR and 1H-NMR spectral studies. The antimicrobial evaluation of the final compounds has proven that they are active against the strains (S. aureus, P. aeruginosa, A. niger, and C. glabrata) incorporating the microdilution method.

Synthesis of thiazole derivatives as cholinesterase inhibitors with antioxidant activity

In the present research, we synthesized two unique series of thiazole compounds having 5-bromothiophene and 3-methylthiophene (2a-2f) in their structure. After that, spectroscopic methods were used to analyze the chemical compositions of the newly synthesized molecules. Then in vitro evaluation was done to determine acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) activity of the synthesized compounds using galantamine as reference standard. The compounds’ antioxidant properties were assessed using DPPH radical scavenging and ferrous ion-chelating techniques. The results of the study showed weak anticholinesterase activity against AChE and BuChE enzymes for all the final compounds. The synthesized analogs also showed significant DPPH radical scavenging activities with IC50 values in the range of 29.16 ± 0.009 to 33.09 ± 0.004 µM (for DDPH) incomparison to standard gallic acid with IC50 = 31.13 ± 0.008 µM (for DDPH). Especially, compound 2c showed the best antioxidant activity with IC50 value of 29.16 ± 0.009 µM.

Design, Synthesis and Evaluation of Pyrrol-thiazole Derivatives as AChE and BuChE Inhibitory and Antioxidant Activities

Thiazole rings are one of the most frequently used heterocyclic moieties and are found in a wide variety of biologically active chemicals. In this research project, we report the synthesis and biological activities of some new thiazole derivatives (2a-2c) as potent anti-Alzheimer’s agents. These final compounds’ structures were characterized by spectral (1H NMR, 13C NMR, and MS spectra) analyses. The highest inhibitory activity against AChE was demonstrated by compound 2c (23.73 ± 0.018 %) with chloro substitution at the meta and para positions of the phenyl ring, while the highest inhibitory activity against BuChE was produced by compound 2a (28.87± 0.003 %) with cyano substitution at the f position of the phenyl ring. Ferrous ion-chelating and DPPH techniques were also used to assess the compounds' antioxidant properties. Compound 2a showed antioxidant effect according to the DPPH method with an IC50 value of 27.18 ± 0.009 µM.

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

Iodine catalyzed oxidative C(CO)–C(methyl) bond cleavage in methyl ketones: Application to the synthesis of β-Carboline-3-esters

A novel synthesis of substituted β-carboline-3-esters was achieved by the molecular iodine catalyzed reaction of tryptophan methyl ester hydrochlorides with methyl ketones through oxidative C(CO) − C(methyl) bond cleavage. The products in these reactions are similar to those produced in regular Pictet-Spengler reactions of tryptophan methyl esters with analogous aldehyde substrates. Studies revealed that, reaction involves iminium formation, cyclization and followed by iodine catalyzed C(CO) − C(alkyl) bond cleavage of methyl group of ketone substrate to the final compound.