Design,Synthesis, and Anticancer Activity of Amide Derivatives of Structurally Modified Combretastatin-A4

A new series of amide derivatives of structurally modified combretastatin-A4 10a–10j are synthesized, and their structures are confirmed by ¹H and ¹³C NMR, and mass spectral data. The products are tested for their anticancer activity towards human cancer cell lines, MCF-7 (breast), A-549 (lung), Colo-205 (colon), and A-2780 (ovarian). The compounds 10b, 10c, and 10d demonstrate the most promising activity.

     

Novel Bis(1,2,4-oxadiazolyl) Fused Thiazole Derivatives: Synthesis and Anticancer Activity

A novel series of bis-1,2,4-oxadiazole fused benzothiazole derivatives 9a–9j are synthesized, and their structures are confirmed by ¹H and ¹³C NMR, and mass spectral data. All products are evaluated in vitro for their anticancer potential against a panel of four human cancer cell lines such as lung cancer (A549), breast carcinoma (MCF-7), melanoma (A375), and colon cancer (HT-29). The combretastatin-A4 is used as standard drug. All compounds 9a–9j exhibit significant anticancer activity with IC₅₀ values ranging from 0.11±0.01 to 14.6±3.89 μM. Among these, compounds 9a–9d, 9h, 9i demonstrate more potent activity than the control.

     

Synthesis and Anticancer Activity of 1,2,3-Triazole Fused N-Arylpyrazole Derivatives

A novel series of triazole derivatives 11a–11j is synthesized. Structures of the products are confirmed by ¹H and ¹³C NMR, and mass spectral data. The anticancer activities of compounds 11a–11j are evaluated against three human cancer cell lines (MCF-7, A549, and A375) using the standard MTT assay in vitro, using doxorubicin as the positive control. All the compounds exhibit significant activity against cancer cell lines. The compounds 11a, 11d, 11e, 11g, and 11j demonstrate more potent activity than the positive control.

     

Synthesis and evaluation of novel 1,2,4-triazolo-[3,4-b]-1,3,4-thiadiazole tethered chalcone hybrids as potential anticancer agents

A series of novel 1,2,4-triazolo-[3,4-b]-1,3,4-thiadiazole tethered chalcone derivatives were designed synthesized by using conventional as well as microwave assisted methods and characterized by ¹H NMR, ¹³C NMR and mass spectral analysis. Microwave assisted synthesis caused an improvement in yield and significant reduction in the reaction time of all the derivatives. All the new synthesized derivatives were further evaluated for their anti-cancer activity against selected four human cancer cell lines; A549 (Lung), MCF-7 (Breast), Colo-205 (Colon) and A2780 (Ovarian). Among the synthesized compounds, 7b , 7c , 7d , 7e , 7g and 7h exhibited potent anticancer activity compared to control drug (etoposide).     

Design,Synthesis, Antimicrobial,and Antioxidant Activity of Dimers of Chromene Containing 1,2,3-Triazole Derivatives Bearing an Alkyl Spacer

A new series of chromene based 1,2,3-triazole derivatives has been synthesized by incorporating biologically active heterocyclic rings containing chromene and triazole moieties in one molecular structure. All newly synthesized compounds are characterized by ¹H and ¹³C NMR, mass, and IR spectra. The title compounds are tested for their activity against different bacterial and fungal strains, and antioxidant activity. Several compounds are determined to be potent antimicrobial and antioxidant agents.

     

Study on the Synthesis and Bioactivity of Novel Mahkoside A Derivatives

Abstract

A series of novel Mahkoside A derivatives was synthesized, and their in vitro cytotoxic activities were evaluated against the human cancer cell line Ec‐9706. A Preliminary structure–activity relationship study showed compounds 7 and 8 have obvious cytotoxic activities (IC₅₀: 30.0 and 12.5 µg · mL^?1, respectively).     

Amide derivatives of 4-azaindole: Design,synthesis, and EGFR targeting anticancer agents

Abstract

A series of amide derivatives of azaindole-oxazoles (11a-n) were designed and synthesized and their structures were confirmed by ¹HNMR, ¹³CNMR and mass spectral analysis. Further, these derivatives were screened for their anticancer activity against human cancer cell lines viz; MCF7 (breast), A549 (lung) and A375 (melanoma). In vitro anticancer activity screening indicated that most of the hybrids exhibited potent inhibitory activities in a variety of cancer cell lines. Among the compounds 11d, 11e, 11f, 11j, 11k, 11l, 11m, and 11n were exhibited more potent activity than standard, in those mainly two compounds 11m and 11j were exhibited excellent activity in MCF-7 cell line with IC₅₀ values 0.034 and 0.036?µM. Moreover, all these compounds were carried out their molecular docking studies on EGFR receptor results indicated that two potent compounds 11m and 11j were strongly binds to protein EGFR (PDB ID: 4hjo). It was found that the energy calculations were in good agreement with the observed IC₅₀ values.     

Synthesis of New Pyrimidine,Quinazoline and Diazatricyclo Derivatives by Multicomponent Reaction and Evaluation of Their Biological Activity

Abstract

A series of new pyrimidine and quinazoline derivatives was synthesized by a Biginelli-like reaction of urea/thiourea, aldehyde, and ketone in the presence of hydrochloric acid as a catalyst. In a similar way, some novel diazatricyclo derivatives were obtained via a Biginelli-like reaction followed by an intramolecular Michael-type addition. The yields of products were reasonable after recrystallization from ethanol. All newly synthesized compounds were characterized using IR and NMR (¹H and ¹³C) spectroscopy and elemental analysis. The antibacterial activity of these compounds was investigated against Staphylococcus aureus (RTCC, 1885), and Escherichia Coli (ATCC, 35922).

Supplemental materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental file.     

Bis-Thiourea Bearing Aryl and Amino Acids Side Chains and Their Antibacterial Activities

Abstract

A series of symmetrical 1,3-bis thiourea 1a–e and 1,4-bis thiourea derivatives 2a–e have been successfully synthesized from the reactions of amines with 3-acetylbenzoyl isothiocyanate and 4-acetylbenzoyl isothiocyanate, respectively. All the synthesized compounds were characterized by FT-IR spectroscopy and ¹H and ¹³C NMR spectroscopy. The compounds were screened for their antibacterial activity by turbidimetric method using gram-negative bacteria (E. coli ATCC 8739) using turbidimetric method. The newly synthesized bis-thiourea derivatives bearing aryl side chains showed good antibacterial activity against E. coli. The effect of the molecular structure of the synthesized compounds on the antibacterial activity is discussed.     

Design,Synthesis, and Biological Evaluation of 2‐(4‐Aminophenyl)benzothiazole Analogues as Antiproliferative Agents

A series of 28 novel 2‐(4‐aminophenyl)benzothiazole analogues have been synthesized and characterized using various analytical techniques like ¹H NMR, ¹³C NMR, electrospray ionization mass spectrometry, and IR and bioevaluated for their antiproliferative activity over a group of three human cancer cell lines, namely, lung cancer (A549), cervical cancer (HeLa), and breast cancer (MDA‐MB‐231), using sulforhodamine B assay method. Few synthesized molecules ( 5a , 5c , 5d , 5f , 7b , and 7j ) displayed effective growth inhibition (GI₅₀) activity against the tested human cancer cell lines at lower micromolar concentration (GI₅₀) values in the range 0.2–1.7 μM. Noticeably, compound 7b exhibited reasonable activity in all three cancer cell lines in the GI₅₀ range 0.55–1.2 μM. Further, when 7b was screened for tubulin polymerization inhibition, it exhibited more than 55% inhibition at concentration of 5.0 μM. The molecular docking simulations supported the molecular interactions of the derivatives with the targeted receptor. These derivatives may serve as lead structures for development of potential anticancer drug candidates, and 7b might act as a potential microtubule polymerization inhibitor.     

Utilization of 2-substituted 3, 1-benzoxazin-4-ones in synthesis of some quinazoline annulated derivatives

Abstract

In this study, a new series of quinazoline and their annulated derivatives have been synthesized. A number of quiazolinone derivatives substituted at position-3 were prepared from 3, 1-benzoxazinone by the treatment of 3,1-benzoxazinone with different nitrogen nucleophiles such as, hydrazine hydrate, phenylhydrazine, ethanolamine, and cyano acetohydrazide afforded the quinazolinone derivatives 7–11. The reaction of hydrazide derivative 5 with aromatic aldehydes gave the Schiff’s bases derivative 16a–c. Some of the synthesized compounds were tested against the breast cancer cell line (MCF-7). The structures of all the newly synthesized compounds were established based on IR, ¹H, ¹³C NMR, mass spectral data, and elemental analyses.     

Synthesis,Antitumor Activity,and SAR of N-Substituted γ-Aminopropylsilatrane Derivatives

Abstract

γ-Aminopropylsilatrane has been reported to possess biological activity against tumor cancer cells with low cytotoxicity in many kinds of silatranes. So some N-substituted γ-aminopropylsilatrane derivatives were synthesized and assayed by a primary anticancer screening against HT-29, Hela, and MDAMB435 cells by the use of the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) method. The structures of these derivatives were confirmed by ¹H NMR, electrospray ionization-mass spectrometry, and elemental analysis. The structure–activity relationship showed that the N-substituted derivatives exhibit better activity in which the γ-amino group of the silatrane is connected with stronger electron-withdrawing groups.     

Synthesis and Antimicrobial Activities of Some 1-[(N,N-Disubstitutedthiocarbamoylthio)acetyl]-3,5-diaryl-2-pyrazolines

The increasing clinical importance of drug-resistant fungal and bacterial pathogens has lent additional urgency to microbiological research and new antimicrobial compound development. For this purpose, new pyrazoline derivatives were synthesized and evaluated for antimicrobial activity.

Some 1-[(N, N-disubstitutedthiocarbamoylthio)acetyl]-3,5-diaryl-2-pyrazolines derivatives were synthesized by reacting 1-(chloroacetyl)-3,5-diaryl-2-pyrazolines with appropriate potassium salts of secondary amine dithiocarbamic acids. The chemical structures of the compounds were elucidated by IR, ¹ H-NMR, and FAB⁺-MS spectral data. Their antimicrobial activities against Staphylococcus aureus (B-767), Escherichia coli (B-3704), Pseudomonas aeruginosa (ATCC 27853), Proteus vulgaris (NRLL B-123), and Candida albicans (NRRL-27077) were investigated. The results showed that some of the compounds have notable activity against S. aureus and C. albicans.     

Synthesis,biological evaluation and molecular docking studies of novel 2-(2-cyanophenyl)-N-phenylacetamide derivatives

A series of novel 2-(2-cyanophenyl)-N-phenylacetamide derivatives 3(a-u) were designed and synthesized via selective amidation of methyl-2-(2-cyanophenyl)acetates over amidine formation by using AlMe₃ as catalyst in good yields. All the newly synthesized derivatives were well characterized by ¹H NMR, ¹³C NMR, FTIR and HRMS spectral techniques. All the synthesized title compounds were evaluated for their in vitro anticancer activity against three cancer cell lines. Among all compounds, 3i (IC₅₀?=?1.20 μM, IC₅₀?=?1.10 μM), 3j (IC₅₀?=?0.11 μM, IC₅₀?=?0.18 μM), 3o (IC₅₀?=?0.98 μM, IC₅₀?=?2.76 μM) showed excellent inhibitory activity than the standard Etoposide (IC₅₀?=?2.11 μM, IC₅₀?=?3.08 μM) against MCF-7 and A-549 cell lines, respectively. Docking analysis of all the compounds with the human topoisomerase II revealed that the compound 3j fitted well in the active site pocket, showing the best docking score of 158.072 kcal/mol.

     

Synthesis and Inhibitory Activity Evaluation of 2,6‐Disubstituted Purine Derivatives

A series of novel 2,6‐disubstituted purine derivatives were designed and synthesized from 2,6‐dichloropurine. The structures of target compounds were determined by ¹H‐NMR, ¹³C‐NMR, and HRMS. The synthesized compounds were evaluated for their inhibitory activities against lung cancer cell lines of A549 and liver cancer cell lines of Bel‐7402. 2‐(4‐Benzyloxy‐phenylamino)‐6‐(cyclohexylamino)purine( 3 ), 2‐(4‐chloro‐phenylamino)‐6‐(n‐butylamino)purine ( 5 ), 2‐(4‐morpholinoamino)‐6‐(4‐hydroxy‐phenylamino)purine ( 9 ), and 2‐(4‐O‐galactosyl‐phenylamino)‐6‐(cyclohexylamino)purine ( 12 ) exhibited moderate inhibitory activity.     

Synthesis,anticancer and antimicrobial evaluation of new pyridyl and thiazolyl clubbed hydrazone scaffolds

Abstract

A series of new hydrazones bearing pyridyl and thiazolyl scaffolds have been synthesized and evaluated for their in vitro anticancer and antimicrobial activities. The anticancer activity was evaluated against the A549 lung cancer cell line. The eight hydrazone derivatives have shown better anticancer activity than positive control doxorubicin against the A549 lung cancer cell line. The antimicrobial activity was evaluated against bacterial and fungal pathogens by using well diffusion method. The four hydrazone derivatives have displayed good antimicrobial activities. Molecular docking studies of the synthesized hydrazone derivatives revealed good binding via hydrogen bond interactions with key residues on active sites as well as neighboring residues with an active site of Focal adhesion kinase (PDB ID 2JKO). A computational study for the prediction of absorption, distribution, metabolism, and excretion (ADME) properties of all compounds has also been performed.     

Synthesis and Antimicrobial Activities of Novel Series of 1-((4-Methyl-2-Substituted Thiazol-5-yl)Methyleneam INO)-2-Substituted Isothiourea Derivatives

A novel series of 1-((4-methyl-2-substituted thiazol-5-yl)methyleneamino)-2-substituted isothiourea derivatives was synthesized by alkylation of (Z/E)-1-((4-methyl-2-substituted thiazol-5-yl)methylene)thiosemicarbazide with alkylhalide in acetone. All the newly synthesized compounds were characterized by spectral (IR, ¹H NMR, ¹³C NMR, and mass spectrometry) methods. The newly synthesized compounds were screened for in vitro antimicrobial activity. Most of the compounds show moderate to excellent antimicrobial activity.

[Supplementary materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfer, and Silicon and the Related Elements for the following free supplemental files: Additional figures and tables.]     

Synthesis,biological screening,in silico study and fingerprint applications of novel 1, 2, 4-triazole derivatives

A series of novel 1,2,4 triazole derivatives were synthesized by treating 4-bromo-2-(4H-1,2,4-triazole-3-yl)aniline (4) with different substituted benzene sulfonyl chlorides 5(a-f) and benzyl bromides 7(a-e) . IR, ¹H-NMR, ¹³C-NMR, and mass analysis confirmed the structures of the newly synthesized compounds. All derivatives were screened for their in vitro antibacterial activity against two bacterial strains viz Escherichia coli and Staphylococcus aureus, antifungal activity against Aspergillus flavus and Candida albicans, anthelmintic activity against Pheretima posthuma and also cytotoxicity activity against MDA-MB 231 and A375 cancer cell lines. It was found that some of the derivatives showed significant antibacterial, antifungal, anthelmintic, and cytotoxic activities when compared to respective standard drugs. Molecular docking studies have assisted the theoretical binding mode of the target molecules. Compounds were also explored for fingerprint application.     

Synthesis,Structure–Activity Relationship of Some New Triorganotin(IV) Derivatives of Dipeptides as Anti-Inflammatory Agents

Abstract

New triorganotin(IV) derivatives of dipeptides with general formulae, R₃Sn(HL), where R = Me and Ph, and HL is the monoanion of histidinylalanine and histidinylleucine, have been synthesized and characterized on the basis of infrared (IR), multinuclear NMR (¹H, ¹³C, and ¹¹⁹Sn), and ¹¹⁹Sn Mössbauer spectroscopic studies. These derivatives exhibit distorted trigonal-bipyramidal geometry around tin in which dipeptide anion acts as bidentate ligand coordinating through carboxyl oxygen and amino nitrogen. Ph₃Sn(HHis-Ala),

Ph₃Sn(HHis-Leu), and previously reported Ph₂Sn(His-Ala), Me₂Sn(His-Ala), n-Oct₂Sn(His-Ala), Me₂Sn(His-Leu), n-Oct₂Sn(His-Leu), Ph₃Sn(HTyr-Phe), Ph₂Sn(Tyr-Phe), Bu₂Sn-(Tyr-Phe), and n-Oct₂Sn(Tyr-Phe) along with standard drugs, viz. phenyl butazone and indomethacin were screened for in vivo anti-inflammatory activity and acute toxicity (LD₅₀). Diorganotin(IV) derivatives are more active than triorganotin(IV) derivatives. Me₂Sn(His-Leu) shows the highest activity.

Supplemental materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental file.     

Synthesis and Antiviral Activity of Novel Thieno[2,3-d]pyrimidine Hydrazones and Their C-Nucleosides

A hydrazinylthienopyrimidine derivative reacted with a number of monosaccharides in the presence of a catalytic amount of acetic acid giving the corresponding sugar hydrazones, that undergo oxidative cyclization under the action of ferric chloride with formation of triazolo derivatives. Structures of the products have been elucidated from IR, ¹H, and ¹³C NMR data. Antiviral activity of the newly synthesized compounds is tested against influenza virus H5N1.