New Compounds from the Roots and Stems of Trigonostemon lii and Their Cytotoxic Activities

A new carboline alkaloid, Trifiline D ( 1 ) and a new degraded diterpenoid, Trigoxyphin X ( 4 ) were isolated from the roots and stems of Trigonostemon lii. Their structures were elucidated by extensive spectroscopic analyses including 1D‐ and 2D‐NMR techniques. Compound 1 exhibited weak inhibitory activity against MCF‐7, A‐549, MGC‐803, and COLO‐205 with IC₅₀ values ranging from 27.4 to 35.4 μm .     

A New Isoflavanol from the Fruits of Kotschya strigosa (Fabaceae)

The phytochemical investigation of the MeOH extract from fruits of Kotschya strigosa using repeated normal and reversed‐phase column chromatography and Sephadex LH‐20 chromatography led to the isolation and characterization of a new isoflavanol, named kotstrigoisoflavanol ( 1 ), together with three known compounds, diosmetin ( 2 ), β‐sitosterol ( 3 ), and the 3‐O‐β‐d‐glucopyranoside of β‐sitosterol ( 4 ). The antioxidant activity of crude extract, 1, and 2 was determined using the 2,2‐diphenyl‐1‐picrylhydrazyl (DPPH˙) method. The crude extract (IC₅₀ 61.7 ± 0.2 μg/ml) and 2 (IC₅₀ 70.2 ± 0.1 μg/ml) showed moderate antioxidant activities, while 1 was weakly active (IC₅₀ 153.1 ± 0.1 μg/ml), as compared with the standard reference l ‐ascorbic acid (IC₅₀ 21.9 ± 0.0 μg/ml).     

Synthesis and In Vitro Urease Inhibition of Some Novel Benzimidazole‐based Hydrazones

A novel series of N′‐(substituted benzylidene)‐2‐(5,6‐dichloro‐2‐methyl‐1H‐benzimidazol‐1‐yl)acetohydrazides and N′‐(1‐(substituted phenyl)ethylidene)‐2‐(5,6‐dichloro‐2‐methyl‐1H‐benzimidazol‐1‐yl)acetohydrazides were synthesized and then studied for their urease inhibitory activities using thiourea as a standard drug. All newly synthesized compounds were found to exhibit potent inhibitory properties against urease enzyme in the range of IC₅₀ = 0.0155 ± 0.0039–0.0602 ± 0.0071 μM, when compared with the thiourea as standard (IC₅₀ = 0.5115 ± 0.0233 μM). All target molecules were characterized by ¹H‐NMR, ¹³C‐NMR, IR, and electrospray ionization mass spectrometry.     

Seco‐Tremulanes from Cultures of the Basidiomycete Flavodon flavus BCC 17421

A new seco‐tremulane, 11,12‐epoxy‐5,6‐secotremula‐1,6(13)‐dien‐5,12‐olide ( 1 ), was isolated together with the known compounds, conocenolides A ( 2 ) and B ( 3 ), tremulenediol A ( 4 ), tremulenolide A ( 5 ), and two lanostane triterpenoids, trametenolic acid B ( 6 ), and pinicolic acid A ( 7 ), from cultures of the basidiomycete Flavodon flavus BCC 17421. Interconversion of conocenolides A/B was demonstrated. Compound 1 exhibited weak cytotoxic activities, whereas tremulenediol A showed antiplasmodial activity (IC₅₀ 8.6 μg/ml). Pinicolic acid A exhibited activity against herpes simplex virus type‐1 (IC₅₀ 15 μg/ml) as well as cytotoxic activities.     

Synthesis and Anti‐proliferative Activity of Novel Polysubstitued Indazole Derivatives

A simple and efficient process is developed for the synthesis of new N‐(1‐alkyl‐3‐chloro‐4‐ethoxy‐1H‐indazol‐5‐yl)‐arylsulfonamides 4a – d and N‐(1‐alkyl‐3‐chloro‐1H‐indazol‐5‐yl)‐arylsulfonamides 5a – d through the reduction of 1‐alkyl‐3‐chloro‐5‐nitroindazoles 2a , b with SnCl₂ in ethanol followed by coupling the corresponding amine with arylsulfonyl chlorides in pyridine. All the newly synthesized compounds have been characterized by elemental analysis and spectroscopic data. Some compounds were tested for their in vitro antiproliferative activities against two selected human cancer cell lines A2780 and A549. Among all of these derivatives, compound 5d showed the most potent antiproliferative activity against A2780 (IC₅₀ = 5.47 ± 1.45 μM) and A549 (IC₅₀ = 7.73 ± 1.66 μM) cell lines.     

Et3N‐Prompted Efficient Synthesis of Anthracenyl Pyrazolines and Their Cytotoxicity Evaluation against Cancer Cell Lines

A series of anthracenyl pyrazoline derivatives ( 3a – o ) were synthesized with an aim to evaluate their in vitro anticancer activities. Anthracenyl pyrazoline compounds were prepared by the reaction between various anthracenyl chalcones ( 1a – o ) and hydrazine hydrate ( 2 ). The reactions were carried out under reflux in the presence of triethylamine and ethanol for 24 h, and the obtained yields were from good to excellent (90–97%). The structure of each compound is well characterized by IR, ¹H‐NMR, ¹³C‐NMR, elemental analyses, and mass spectroscopic technics, and the molecular structures of compounds 3d and 3e were solved by single‐crystal X‐ray crystallographic methods. The newly synthesized compounds ( 3a – o ) were evaluated for their in vitro cytotoxic studies against four human cancer cell lines MCF‐7 (breast cancer cell lines), SK‐N‐SH (neuroblastoma cancer cell lines), HeLa (cervical cancer cell lines), and HepG2 (liver cancer cell lines), and the screening results show strong cytotoxic effects for most of the synthesized compounds against the three cell lines except SK‐N‐SH cells. Notably, compounds 3a , 3j , 3l , 3m , 3n , and 3o showed a highly potential activity against HeLa cells (IC₅₀: 0.22, 0.3, 0.3, 0.10, 0.25, and 0.25 μM), while compounds 3i , 3k , 3l , and 3m showed a significant cytotoxic activity in HepG2 cells (IC₅₀: 0.22, 0.44, 0.40, and 0.22 μM), whereas compounds 3a , 3b , 3d , and 3e exhibit a promising cytotoxicity against MCF‐7 cells (IC₅₀: 0.73, 0.495, 0.493, and 0.66 μM).     

Green synthesis and characterizations of Nickel oxide nanoparticles using leaf extract of Rhamnus virgata and their potential biological applications

In the present report, Nickel oxide nanoparticles (NiONPs) were synthesized using Rhamnus virgata (Roxb.) (Family: Rhamnaceae) as a potential stabilizing, reducing and chelating agent. The formation, morphology, structure and other physicochemical properties of resulting NiONPs were characterized by Ultra violet spectroscopy, X‐ray diffraction (XRD), Fourier Transform Infrared analysis (FTIR), Scanning electron microscopy (SEM), Energy‐dispersive‐spectroscopy (EDS), Transmission electron microscopy (TEM), Raman spectroscopy and dynamic light scattering (DLS). Detailed in vitro biological activities revealed significant therapeutic potential for NiONPs. The antimicrobial efficacy of biogenic NiONPs was demonstrated against five different gram positive and gram negative bacterial strains. Klebsiella pneumoniae and Pseudomonas aeruginosa (MIC: 125 μg/mL) were found to be the least susceptible and Bacillus subtilis (MIC: 31.25 μg/mL) was found to be the most susceptible strain to NiONPs. Biogenic NiONPs were reported to be highly potent against HepG2 cells (IC₅₀: 29.68 μg/ml). Moderate antileishmanial activity against Leishmania tropica (KMH₂₃) promastigotes (IC₅₀: 10.62 μg/ml) and amastigotes (IC₅₀: 27.58 μg/ml) cultures are reported. The cytotoxic activity was studied using brine shrimps and their IC₅₀ value was recorded as 43.73 μg/ml. For toxicological assessment, NiONPs were found compatible towards human RBCs (IC₅₀: > 200 μg/ml) and macrophages (IC₅₀: > 200 μg/ml), deeming particles safe for various applications in nanomedicines. Moderate antioxidant activities: total antioxidant capacity (TAC) (51.43%), 2,2‐diphenyl‐1‐picrylhydrazyl (DPPH) activity (70.36%) and total reducing power (TRP) (45%) are reported for NiONPs. In addition, protein kinase and alpha amylase inhibition assays were also performed. Our results concluded that Rhamnus virgata synthesized NiONPs could find important biomedical applications with low cytotoxicity to normal cells.     

Synthesis of Novel 1,2,4‐Triazole‐3‐thione Derivatives as Influenza Neuraminidase Inhibitors

A series of 1,2,4‐triazole‐3‐thione derivatives ( 6a – 6t ) were synthesized and evaluated against influenza viruses (H1N1) neuraminidase (NA) in vitro. Eighteen compounds exhibited inhibitory potency with IC₅₀ values ranging from 14.68 ± 0.49 to 39.85 ± 4.23 μg/mL. Among them, compounds 6e and 6h showed significant inhibitory activity with IC₅₀ values of 14.97 ± 0.70 and 14.68 ± 0.49 μg/mL, respectively. Structure activity relationships were established. Molecular docking studies were performed to understand the binding interaction between active compounds and NA.     

Regioselective Reactions,Spectroscopic Characterization,and Cytotoxic Evaluation of Spiro‐pyrrolidine Thiophene

Spiro‐oxo‐indole/pyrrolidine‐thiophene base possessed significant pharmacological activity. The [3 + 2] cycloaddition reactions of thia‐methine ylide respected through multi‐component reaction affording regioselective and stereoselective spiroindoline‐3,2′‐tetrahydrothiophene derivative 3 . Reaction of such compound with different electrophilic and nucleophilic reagents afforded bioactive heterocyclic compounds 4 – 16 . Biological evaluation showed that these synthesized spiro‐pyrrolidine exhibited moderate to good cytotoxic activity. Among them, compounds 7 and 14 displayed the best cytotoxic activity against MCF‐7 and Wl‐38 cells with the IC₅₀ values of 7.02 ± 0.6 and 8.97 ± 0.9 μm (very strong), respectively. Compounds 4 , 5 , and 12 exhibited strong cytotoxicity's with IC₅₀ 16.28 ± 1.7, 11.16 ± 1.1, and 19.14 ± 1.7 μm, respectively, against MCF‐7 mammary gland cell line. All compound structures were supported by spectroscopic data and elemental analysis.     

Two New Flavonoids from Derris eriocarpa How

Two new flavonoids, 1 and 2 , together with two known flavonoids, tephrosin ( 3 ) and 12a‐hydroxy‐α‐toxicarol ( 4 ), were isolated from the whole herb of Derris eriocarpa How . The structures and absolute configurations of the new compounds were elucidated on the basis of their MS, NMR, and ECD data. The structures of the known compounds were established by extensive spectroscopic (MS, 1D‐ and 2D‐NMR) analyses and comparison with the literature data. All compounds were isolated from D. eriocarpa for the first time. Compound 3 showed modest inhibitory activities against the growth of human cancer cells HEL and A549 with the IC₅₀ values of 15.03 ± 0.62 and 13.27 ± 0.39 μm , respectively.     

Synthesis of Substituted Quinolinyl Ether‐based Inhibitors of PI3K as Potential Anticancer Agents

A new strategy for the preparation of 8‐quinolyl ethers 3 ( a – g ), 5 ( a – g ), and 7 ( a – d ) was studied by copper (II)‐catalyzed methodology in the presence of Cs₂CO₃ and acetone–water mixture (1:1). Screening of quinolinyl‐8‐ethers was investigated against anticancer expressive studies to validate new chemical entity in medicinal chemistry. Approaches were evaluated against breast cancer (MCF‐7), skin cancer (G‐361), and colon cancer (HCT 116) cell lines. Inhibitory potentials against phosphoinositide‐3‐kinase (PI3K) enzyme responsible for cancer development have been evaluated by competitive ELISA studies. In PI3K assay, 3a – c were inactive (IC₅₀ > 5 μM), while 3e – g , 5a , 5c – e , 5g , 7a , and 7d showed a moderate activity (IC₅₀ ≥ 0.05 μM). Compounds ( 5b , 5f , 7b , and 7c ) showed significant activity (IC₅₀ < 1.0 μM); thus, their anticancer activities were carried out. Anticancer activity was found to be selective towards breast cancer (MCF‐7); 5b , 5f , 7b , and 7c showed predominant relative percentage activities of 74.12%, 79.04%, 72.56%, and 78.47%, with IC₅₀ values of 5b (2.27 ± 0.88 μM), 5f (1.38 ± 0.60 μM), 7b (2.64 ± 0.86 μM), and 7c (1.87 ± 0.68 μM) compared with the standard doxorubicin 73.14% inhibition (IC₅₀ = 1.98 ± 0.75 μM). Docking study also conducted to find out the binding interactions with p110α (PDB ID: 3T8M) enzyme. Compounds 5b , 5f , 7b , and 7c showed best docking score into the active site of PI3K 12.59, 10.51, 56.52, and 8.61 nM. Structure–activity relationship studies demonstrated that the synthesized compounds are the potential PI3K inhibitors to treat various cancer‐related diseases.     

Anti‐inflammatory Exploration of Sulfonamide Containing Diaryl Pyrazoles with Promising COX‐2 Selectivity and Enhanced Gastric Safety Profile

Novel sulfonamide containing diaryl pyrazoles were synthesized and were subsequently tested for their in vitro cyclooxygenase inhibitory assay. Compounds that showed promising in vitro COX‐2 IC₅₀ values and selectivity indices were then evaluated for their in vivo anti‐inflammatory inhibition assay using standard carrageenan‐induced rat paw edema method. Two promising inhibitors were evaluated for ulcerogenic liability. X‐ray crystal structure of COX‐2 was taken from PDB entry COX‐2 (3LN1) having a resolution of 2.80 Å (Angstroms). Structural preparations for docking studies were accomplished using protein preparation wizard in Maestro 9.0. Compound 10b displayed reasonable COX‐2 inhibition (COX‐2 IC₅₀ = 0.52 μM) and COX‐2 selectivity index (SI = 10.73) when compared with celecoxib (COX‐2 IC₅₀ = 0.78 μM) and (SI = 9.51). In vivo anti‐inflammatory studies demonstrated 64.28% inhibition for 10b in comparison with the 57.14% for that of celecoxib itself. The results of ulcerogenic liability were also found comparable with standard celecoxib. Molecular docking studies revealed that all the designed molecules showed good interactions with receptor active site with glide scores in the range −13.130 to −10.624.     

Synthesis,Antimicrobial, and Anticancer Activities of a New Series of Thieno[2,3‐d] Pyrimidine Derivatives

A new series from thieno[2,3‐d] pyrimidine derivatives have been synthesized based on 2‐(ethylmercapto)‐4‐mercapto‐6‐phenyl‐5‐pyrimidine carbonitrile, these compounds used in the synthesis of many pyrimidothienopyrimidine derivatives and triazolo[1″,5″:1″,6″]pyrimido[4′,5′:4,5]thieno[2,3‐d] pyrimidine derivatives. The chemical composition of these compounds was confirmed by ¹H NMR, ¹³C NMR, and MS techniques. Some of the synthesized compounds were screened for their antimicrobial and anticancer agent. Compound ( 9b ) showed strong effect on Aspergillus Fumigatus (RCMB 2568), Candida albicans (RCMB 05036), Saphylococcus aureus (RCMB 010010), Bacillis subtilis (RCMB 010067), Salmonella sp. (RCMB 010043), and Escherichia coli (RCMB 010052). Compounds ( 2 ) and ( 5a – k ) were evaluated for their IC₅₀ values against two cancer cell lines (MCF‐7 and HeLa cells) in the presence of Paclitaxel as reference material. Compound ( 5g ) showed the highest cytotoxicity against MCF‐7 (IC₅₀ values about 18.87 ± 0.2 μg/mL) cells compared with Paclitaxel (IC₅₀ values about 40.37 ± 1.7 μg/mL). Also, compound ( 5d ) showed the highest cytotoxicity against HeLa (IC₅₀ values about 40.74 ± 1.7 μg/mL) cells compared with Paclitaxel (IC₅₀ values about 45.78 ± 0.8 μg/mL).     

Ciprofloxacin/Gatifloxacin‐1,2,3‐triazole‐isatin Hybrids and Their In Vitro Anticancer Activity

Eleven novel ciprofloxacin/gatifloxacin‐1,2,3‐triazole‐isatin hybrids ( 8a – k ) were designed, synthesized, and screened for their in vitro anticancer activity in this paper. A significant part of the synthesized hybrids was active against A549, HepG2, and SF‐268 cancer cell lines, whereas the parent drugs ciprofloxacin and gatifloxacin were devoid of activity. Among them, hybrid 8i (IC₅₀: 78.1–90.7 μM) was found to be the most active against A549, HepG2, and SF‐268 cancer cell lines, and it was comparable with or better than Vorinostat (IC₅₀: 71.1 to >100 μM). Thus, these kind hybrids have potentiality for discovery of new anticancer candidates for clinical deployment in the control and eradication of cancers.     

Three New Alkaloids from the Leaves of Uncaria rhynchophylla

Three new alkaloids, 2′‐O‐β‐D ‐glucopyranosyl‐11‐hydroxyvincoside lactam ( 1 ), 22‐O‐demethyl‐22‐O‐β‐D ‐glucopyranosylisocorynoxeine ( 2 ), and (4S)‐corynoxeine N‐oxide ( 3 ) were isolated from the leaves of Uncaria rhynchophylla, together with four known tetracyclic oxindole or indole alkaloids, isocorynoxeine N‐oxide ( 4 ), rhynchophylline N‐oxide ( 5 ), isorhynchophylline N‐oxide ( 6 ), and dihydrocorynantheine ( 7 ), and an indole alkaloid glycoside, strictosidine ( 8 ). The structures of 1 – 3 were elucidated by spectroscopic methods including UV, IR, ESI‐TOF‐MS, 1D‐ and 2D‐NMR, as well as CD experiments. The activity assay showed that 8 (IC₅₀=8.3 μM ) exhibited potent inhibitory activity on lipopolysaccharide(LPS)‐induced nitrogen monoxide (NO) release in N9 microglia cells. However, only weak inhibitory activities were observed for 1 – 7 (IC₅₀>100 μM for 1 – 6 or >30 μM for 7 ).     

Evaluation of newly synthesized derivatives of bis(hydrazine‐1‐carbothioamide) and their metal complexes synthesized in bulk and nano size as potent anticancer agents

A series of new metal complexes were synthesized in both bulk and nano size using green methods, starting with the reaction of (E)‐N′‐[(E)‐2‐bromobenzylidene]‐4‐oxo‐4‐(piperidin‐1‐yl)but‐2‐enehydrazide with thiosemicarbazide and different metal halides such as CuI·2H₂O, CuCl₂·2H₂O, CoCl₂·2H₂O, and ZnCl₂·2H₂O, and metal nitrate such as Ga(NO₃)₃·2H₂O. Structures of these metal complexes were confirmed using different spectroscopic methods, elemental analysis, electronic spectra, and microanalytical methods (scanning electron microscopy and transmission electron microscopy) for nano complexes. The distorted octahedral geometry for all complexes was suggested based on magnetic moments and electronic spectral studies. The cytotoxic activity of the compounds was investigated against human hepatocellular carcinoma (HepG2) and human colorectal carcinoma (HCT‐116) cell lines. Most tested compounds had higher inhibitory activity than the standard vinblastine drug. Interestingly, the nano‐sized Ga(III) complex 11 was the most potent compound against the two tested cell lines, with 50% inhibitory concentration (IC₅₀) of 2.56 μg/mL for HepG2, compared with the reference drug vinblastine (IC₅₀ 15.6 μg/mL), and IC₅₀ 4.64 μg/mL for HCT‐116, compared with the standard (IC₅₀ 13.9 μg/mL). The bioassay results helped us identify new potent and selective anticancer agents.     

Design,synthesis of (Z)‐3‐benzyl‐5‐((1‐phenyl‐3‐(3‐((1‐ substituted phenyl‐1H‐1,2,3‐triazol‐4‐yl)methoxy)phenyl)‐1H‐pyrazol‐4‐yl)methylene)thiazolidine‐2,4‐dione analogues as potential cytotoxic agents

In an attempt to achieve promising cytotoxic agents, a series of new (Z)‐3‐benzyl‐5‐((1‐phenyl‐3‐(3‐((1‐substituted phenyl‐1H‐1,2,3‐triazol‐4‐yl)methoxy)phenyl)‐1H‐pyrazol‐4‐yl)methylene)thiazolidine‐2,4‐diones 10 a‐n were designed, synthesized, and characterized by ¹H NMR, ¹³C NMR, IR, and ESI‐MS techniques. These compounds synthesized from appropriate reaction procedures with better yields. All the novel synthesized compounds 10a‐n were evaluated for their cytotoxic activity against the MCF‐7 cell line (Human breast cancer cell line) at different concentrations of 0.625, 1.25, 2.5, 5, and 10 μM, respectively. The cytotoxic evaluation assay is presented in terms of IC₅₀ values and percentage cell viability reduction compared against standard drug cisplatin. Among all novel synthesized compounds 10a‐n , some of the representative analogues particularly 10g and 10e exhibit remarkable cytotoxic activity with IC₅₀ values 0.454 and 0.586 μM, comparable to that of the standard drug cisplatin, and some analogues 10d , 10f , 10k, and 10m also have shown significant activity.     

Microwave‐Assisted Synthesis and Antituberculosis Screening of Some 4‐((3‐(Trifluoromethyl)‐5,6‐dihydro‐[1,2,4]triazolo[4,3‐a]pyrazin‐7(8H)‐l)methyl)benzenamine Hybrids

In the present investigation, a series of 4‐((3‐(trifluoromethyl)‐5,6‐dihydro‐[1,2,4]triazolo[4,3‐a]pyrazin‐7(8H)‐yl)methyl)benzenamine analogs 6a–o were synthesized and characterized by IR, NMR (¹H and ¹³C), and mass spectra. All newly synthesized compounds 6a–o were prepared under conventional and microwave irradiation methods. These compounds obtained in higher yields and in shorter reaction times in the microwave irradiation method when compared with the conventional method. Synthesized compounds 6a–o were inspected for their in vitro antitubercular activity against Mycobacterium tuberculosis H₃₇Ra using an established XTT reduction menadione assay. Among the screened compounds, 6i (IC₅₀: 1.82 μg/mL), 6j (IC₅₀: 1.02 μg/mL), and 6k (IC₅₀: 1.59 μg/mL) showed excellent activity. Furthermore, compound 6i showed MIC₉₀ value of 16.02 μg/mL. In summary, the results indicate the identification of some novel, selective, and specific inhibitors against M. tuberculosis that can be explored further for the potential antitubercular drug.     

Unusual coordination mode of aroyl/acyl thiourea ligands and their π‐arene ruthenium (II) piano‐stool complexes: Synthesis,molecular geometry,theoretical studies and biological applications

Two mononuclear ruthenium complexes ( 1 and 2 ) with aroyl/acylthiourea as an ancillary ligand of type, [(η⁶‐p‐cymene)RuCl(L‐N,S)], where [ L1  = 2,4‐dichloro‐N‐(o‐tolylcarbamothioyl)benzamide] and L2  = N‐(phenylcarbamothioyl)cyclohexanecarboxamide] were synthesized and well characterized. The single crystal X‐ray diffraction studies revealed the coordination mode and the geometry of the complexes. The two complexes adopted general piano‐stool (three‐legged) geometry with a novel coordination mode of aroyl/acylthiourea through amide N (anionic) and thiocarbonyl S (neutral). This type of monobasic bidentate coordination of the aroyl/acylthiourea ligand was witnessed the first time around the metal ion. The coordination of the complexes was well explained through geometric parameters and frontier molecular orbital parameter values computed at the B3LYP/SDD level. The synthesized complexes were also screened for their antibacterial, antifungal, antioxidant and in vitro antiproliferative activities. Complexes exhibited good antimicrobial agents against various pathogens. The antioxidant activity of the complex 2 has shown most potent activity with IC₅₀ value of 48.55 ± 1.7 μM compared to the reference drug. In addition, the in vitro antiproliferative activity of the complex 2 showed excellent activity against HepG‐2 cell line with the IC₅₀ value of 24.30 ± 1.20 μM which is close to Doxorubicin standard drug.