Recent Advancements and Future Prospects in NBD-Based Fluorescent Chemosensors: Design Strategy, Sensing Mechanism, and Biological Applications.

In recent years, the field of Supramolecular Chemistry has witnessed tremendous progress owing to the development of versatile optical sensors for the detection of harmful biological analytes. Nitrobenzoxadiazole (NBD) is one such scaffold that has been exploited as fluorescent probes for selective recognition of harmful analytes and their optical imaging in various cell lines including HeLa, PC3, A549, SMMC-7721, MDA-MB-231, HepG2, MFC-7, etc. The NBD-derived molecular probes are majorly synthesized from the chloro derivative of NBD via nucleophilic aromatic substitution. This general NBD moiety ligation method to nucleophiles has been leveraged to develop various derivatives for sensing analytes. NBD-derived probes are extensively used as optical sensors because of remarkable properties like excellent stability, large Stoke's shift, high efficiency and stability, visible excitation, easy use, low cost, and high quantum yield. This article reviewed NBD-based probes for the years 2017-2023 according to the sensing of analyte(s), including cations, anions, thiols, and small molecules like hydrogen sulfide. The sensing mechanism, designing of the probe, plausible binding mechanism, and biological application of chemosensors are summarized. The real-time application of optical sensors has been discussed by various methods, such as paper strips, molecular logic gates, smartphone detection, development of test kits, etc. This article will update the researchers with the in vivo and in vitro biological applicability of NBD-based molecular probes and challenges the research fraternity to design, propose, and develop better chemosensors in the future possessing commercial utility.

The Phytochemical Tactics for Battling Antibiotic Resistance in Microbes: Secondary Metabolites and Nano Antibiotics Methods.

One of the most serious threats to human health is antibiotic resistance, which has left the world without effective antibiotics. While continuous research and inventions for new antibiotics are going on, especially those with new modes of action, it is unlikely that this alone would be sufficient to win the battle. Furthermore, it is also important to investigate additional approaches. One such strategy for improving the efficacy of existing antibiotics is the discovery of adjuvants. This review has collected data from various studies on the current crisis and approaches for combating multi-drug resistance in microbial pathogens using phytochemicals. In addition, the nano antibiotic approaches, are discussed, highlighting the high potentials of essential oils, alkaloids, phenolic compounds, and nano antibiotics in combating antibiotic resistance.

Magnetite-supported montmorillonite (K10) (nanocat-Fe-Si-K10): an efficient green catalyst for multicomponent synthesis of amidoalkyl naphthol.

Montmorillonite (K10) loaded on magnetite silica-coated nanoparticles was made using simple co-precipitation methods. The prepared nanocat-Fe-Si-K10 was analyzed using some techniques including field emission-scanning electron microscopy (FE-SEM), inductive coupling plasma-optical emission spectroscopy (ICP-OES), X-ray diffraction (XRD), thermo-gravimetric analysis (TGA), Fourier transmission-infrared spectra (FT-IR), energy dispersive X-ray spectroscopy (EDS), and wavelength-dispersive spectroscopy (WDX). The catalytic activity of the synthesized nanocat-Fe-Si-K10 has been examined in one-pot multicomponent transformations for the synthesis of 1-amidoalkyl 2-naphthol derivatives under solvent-free conditions. Nanocat-Fe-Si-K10 was determined to be very active, having the ability to be reused 15 times without significant loss of catalytic activity. The suggested technique has several advantages, including excellent yield, minimum reaction time, a straightforward workup, and catalyst recycling, all of which are essential green synthetic aspects.

Marine-derived Natural Products as Anticancer Agents.

Cancer is a deadly human disease on the rise due to changes in lifestyle, nutrition, and global warming. Cancer is characterized by uncontrolled, disordered, and undesired cell division. About 60% of cancer medicines approved by the FDA are made from natural ingredients. Intensive efforts over the last decade to better understand the vast chemical diversity provided by marine life have resulted in an intriguing "marine pipeline" of potential anticancer clinical and preclinical treatments. The molecular targets of marine products as anticancer drugs, as well as different reported compounds acting on distinct targets, are the topic of this review.

Sulphur Containing Heterocyclic Compounds as Anticancer Agents.

After cardiovascular disease, cancer is the most common cause of death worldwide. Due to their versatility, heterocyclic compounds play an important role in drug discovery. Medical remedies are constantly being discovered, especially for catastrophic disorders such as cancer. Here, this review is focused on sulphur containing heterocyclic compounds as anticancer agents. Sulphur is found in a variety of vitamin cofactors, sugars, and nucleic acids, and it also plays a function in controlling translation by sulphurating transfer RNA. Sulphur has obtained a lot of interest in the anticancer research medicinal fields. Thiophene derivatives were tested for anti-proliferative activity against breast cancer cells in a recent screening study, and the bulk of chemicals exhibited potent inhibitory effects. In recent years, azoles such as thiazole and thiadiazole structures have gained prominence in cancer research.

Structure activity relationship (SAR) and anticancer activity of pyrrolidine derivatives: Recent developments and future prospects (A review).

Pyrrolidine molecules are a significant class of synthetic and natural plant metabolites, which show the diversity of pharmacological activities. An extensive variety of synthetic pyrrolidine compounds with numerous derivatization like spirooxindole, thiazole, metal complexes, coumarin, etc have revealed significant anticancer activity. Pyrrolidine molecules are found not only as potential anticancer candidates but also retain the lowest side effects. Depending upon the diverse substitution patterns of the derivatives, these molecules have demonstrated an incredible ability to regulate the various targets to give excellent anti-proliferative activities. Taking these into consideration, efforts have been taken by the scientific fraternity to design and develop a potent anticancer scaffold with negligible side effects. In the present review, we cover the latest advancements in the synthesis of pyrrolidine molecules which have promising anticancer activity toward numerous cancer cell lines. Additionally, it also highlights the effectiveness of derivatives via elucidation of Structural-Activity-Relationship (SAR) which is discussed in detail.

DNA intercalators as anticancer agents.

Cancer is one of the most prevailing disease conditions, which occurs due to uncontrolled cell division either due to natural mutation to the genes or due to changes induced by physical, chemical, or biological carcinogens. According to WHO, it is the second leading cause of death worldwide and has reported 10 million deaths in 2020. Hence, there arises the need for better chemotherapies and DNA intercalators are one such emerging therapy for cancer. DNA intercalating agents reversibly intercalate with the double-helical structure of DNA by interacting with adjacent base pairs and disrupting the structure of DNA and thereby causing cell death. Here, we discuss the different classes of organo-intercalators used in cancer therapy describing their anticancer and intercalation ability by different methods along with their structure-activity relationship and mechanism of action.

Synthesis and photobiological applications of naphthalimide-benzothiazole conjugates: cytotoxicity and topoisomerase IIα inhibition.

Conjugates of naphthalimide, benzothiazole, and indole moieties are synthesized that show excellent cytotoxicity against A549 (lung), MCF7 (breast), and HeLa (cervix) cancer cell lines with IC50 values in the range of 0.14-8.59 µM. Compounds 12 and 13 substituted with ethanolamine and propargyl groups reveal potent cytotoxicity towards A549 cancer cells with IC50 values of 140 and 310 nM, respectively. These compounds are further evaluated as potent inhibitors of human type IIα topoisomerase. These conjugates also reveal strong interaction towards human serum albumin (HSA) with binding constant values of 1.75 × 105 M-1 and 1.88 × 105 M-1, respectively, and formation of the stable complex at ground state with static quenching. Docking studies also confirm the effective interactions between conjugates and topoisomerase.

Dual-channel ratiometric recognition of Al3+ and F- ions through an ESIPT-ESICT signalling mechanism.

An optical probe 1 has been synthesized comprising naphthalimide unit conjugated with Schiff base, exhibiting excited state intramolecular proton transfer and intramolecular charge transfer as a potential sensor for Al3+ and F- ions using standard spectroscopic techniques. The probe 1 exhibited local and charge-transfer excitation at 340 nm and 460 nm, respectively. On excitation at 460 nm, probe 1 displayed two emission bands at 510 nm and 610 nm, accompanied by Stokes' shift of 50 nm and 150 nm, respectively. The solvatochromic effect and theoretical calculation depicted that the representative emissions resulted from the ESICT/ESIPT phenomenon. Upon addition of Al3+ ions, the charge transfer excitation at 460 nm was enhanced ratiometrically to local excitation at 340 nm and showed a color change from orange to yellow. Similarily, probe 1.Al3+ displayed emission enhancement at 540 nm in H2O/CH3CN (1:9; v/v) and showed a color change from yellow to blue-green emission. Following the detection of Al3+ ions, hydrolysis of probe 1 to its reacting precursors was observed. The detection of Al3+ ions was also demonstrated in surfactant-containing water. The limit of detection (LOD) of probe 1 (H2O/CH3CN (1:9; v/v)) towards Al3+ ions was measured to be 3.2 × 10-8 M. The probe 1 displayed a ratiometric absorption response towards F- ions with a new peak at 570 nm and showed a color change from orange to purple. The probe 1.F- displayed a decrease in emission at 635 nm. The LOD of probe 1 (CH3CN) towards F- ions was measured to be 7.5 × 10-7 M.

Copper(I) and silver(I) complexes of anthraldehyde thiosemicarbazone: synthesis, structure elucidation, in vitro anti-tuberculosis/cytotoxic activity and interactions with DNA/HSA.

A reaction of copper(i) halides (X = I, Br, Cl) and silver(i) halides with 9-anthraldehyde thiosemicarbazone (9-Hanttsc, H1L) and triphenylphosphine produced halogen-bridged dinuclear complexes, [M2(µ2-X)2(η1-S-9-Hanttsc)2(Ph3P)2] (M = Cu, X = Cl, 1; Br, 2; I, 3; M = Ag, X = Cl, 4; Br, 5). A similar reaction of 9-anthraldehyde-N1-methyl thiosemicarbazone (9-Hanttsc-N1-Me, H2L) with Ph3P and silver(i) halides yielded sulfur-bridged dimers, [Ag2X2(µ2-S-9-Hanttsc-N1-Me)2(Ph3P)2] (X = Cl, 9; Br, 10), however with copper(i) halides insoluble compounds were formed, which upon the addition of one extra mole of Ph3P gave mononuclear complexes of the formula [CuX(η1-S-9-Hanttsc-N1-Me)(Ph3P)2] (X = Cl, 6; Br, 7; I, 8). All of the complexes have been characterized by elemental analysis, NMR (1H, 13C) spectroscopy and single crystal X-ray crystallography (2, 5, 6, and 9). Both the ligands (H1L and H2L) and their complexes (1-10) were tested for their anti-tubercular and anticancer activities. The interactions of the ligands and their complexes (copper and silver) with calf thymus DNA (ct-DNA) and human serum albumin (HSA) were examined through UV-visible and fluorescence spectroscopy. Results showed that copper complex 2 displayed strong interactions with ct-DNA and HSA having binding constant values of 6.66 × 104 M-1 and 3.28 × 104 M-1, respectively, followed by silver complex 10 which gave binding constant values of 4.60 × 104 M-1 and 3.06 × 104 M-1, respectively. All of the complexes also showed good interactions with DNA in docking studies.

Synthesis, cytotoxicity, pharmacokinetic profile, binding with DNA and BSA of new imidazo[1,2-a]pyrazine-benzo[d]imidazol-5-yl hybrids.

Novel derivatives possessing imidazo[1,2-a]pyrazine and 1H-benzo[d]imidazole scaffolds were synthesized using Suzuki-Miyaura cross-coupling reactions. In vitro anticancer activities against NCI-60 cancer cell panels were tested at 10 µM concentration. The best results were obtained from substitution of two 1-cyclohexyl-1H-benzo[d]imidazole groups present at C-6 and C-8 positions of imidazo[1,2-a]pyrazine (31). Compound 31 was found to be cytotoxic against 51 cell lines and cytostatic against 8 cell lines with broad range of growth inhibitions (-98.48 to 98.86%). GI50 value of compound 31 was found in the range of 0.80-2.87 µM for 59 human cancer cell lines at five-dose concentration levels. DNA binding study of potent compound 31 was suggested that this compound was intercalated into DNA base pairs with binding constant of 1.25 × 104 M-1. Compound 31 showed effective binding with bovine serum albumin (BSA) and presented binding constant value of 3.79 ×104 M-1. Pharmacokinetic studies revealed that all compounds are following Lipinski's rule of five and expected to be orally active.

Spectroscopy and molecular docking approach for investigation on the binding of nocodazole to human serum albumin.

The interaction between nocodazole (Nz) and human serum albumin (HSA) under controlled physiological condition (pH 7.4) is examined using absorption, emission, fluorescence lifetime (FLT) and circular dichroism (CD) spectroscopic techniques. The binding constant (order of 105 M-1) from UV-vis and fluorescence spectroscopy reveals a strong interaction between Nz and HSA. Fluorescence quenching study shows that Nz binds with HSA through static quenching process. It is induced by formation of Nz-HSA complex because the Stern-Volmer quenching constant is inversely correlated with the temperature which is further verified by time-resolved fluorescence spectroscopy. The thermodynamic parameters at different temperatures indicate that the binding process is spontaneous where hydrogen bonding interactions and Van der Waals forces play major roles during the interaction between Nz and HSA. By means of spectroscopy and molecular modeling, we have discovered and interpreted the alteration of the secondary structure of HSA by Nz complexation. Synchronous, three-dimensional fluorescence and CD spectroscopic results reveal that the addition of Nz to HSA affects changes in the micro-environment and conformation of HSA. According to Förster Resonance Energy Transfer (FRET), the binding distance (r) between Nz and residue of HSA is <8 nm with excellent energy efficiency. The docking study suggests that nocodazole binds at Domain IIA in the hydrophobic pocket of human serum albumin.

Synthesis of naphthalimide-phenanthro[9,10-d]imidazole derivatives: In vitro evaluation, binding interaction with DNA and topoisomerase inhibition.

The synthesis and characterization of a series of naphthalimide and phenanthro[9,10-d]imidazole conjugate is described. These compounds are evaluated in vitro for their cytotoxicity towards 60 human cancer cell lines. Derivative 16 shows excellent cytotoxic activity against these cancer cell lines with the range of growth inhibition from -55.78 to 94.53. The most potent derivative (ethylpiperazine, 16) is further studied to evaluate the interaction with ct-DNA using absorption and emission spectroscopy as well as DNA viscosity measurement. The DNA binding studies indicate that compound 16 is significantly interacted with DNA through groove binding having binding constant value of 7.81 × 104 M-1 alongwith partial intercalation between the base pairs of DNA strands. Further, topoisomerase inhibition study suggests that compound 16 is induced apoptosis and inhibits human topoisomerase (Topo-IIα) as a possible intracellular target. Molecular docking study of compound 16 with ct-DNA shows good docking score.

Effective synthesis of benzimidazoles-imidazo[1,2-a]pyrazine conjugates: A comparative study of mono-and bis-benzimidazoles for antitumor activity.

A novel series of 6-substituted-8-(1-cyclohexyl-1H-benzo[d]imidazole-6-yl)imidazo[1,2-a]pyrazine and 6-substituted-8-(1-benzyl-1H-benzo[d]imidazole-6-yl)imidazo[1,2-a]pyrazine is first time synthesized and screen in vitro biological activity for 60 human cancer cell lines representing nine different cancer types. Derivatives 10 and 36 show antitumor activity for all tested cell lines, display comparable full panel mean-graph midpoint growth inhibition (MG_MID GI50) values of 2.10 and 2.23 µM, respectively. Furthermore, these derivatives show strong binding interactions with DNA and bovine serum albumin (BSA), studied through absorption, emission, and circular dichroism techniques. These spectroscopic studies reveal that imidazo[1,2-a]pyrazine-benzimidazoles 10 and 36, intercalate with ct-DNA as a leading interaction for fundamental biologically significant effects, with monobenzimidazole show better activity than bisbenzimidazole. These experiments have confirmed that the imidazo[1,2-a]pyrazine and benzimidazole moieties are efficient pharmacophores to trigger binding to DNA. These compounds have also interacted with bovine serum albumin protein that demonstrating high values of binding constant.

Synthesis and in vitro evaluation of naphthalimide-benzimidazole conjugates as potential antitumor agents.

A series of novel naphthalimide-benzimidazoles was designed and synthesized for the first time and studied for their effect on antiproliferative activity. Some of these compounds possessed good antitumor activity towards the tested cancer cell lines. Noticeably, (diethylamino)ethyl 15 and (dimethylamino)ethyl 23 derivatives displayed superior antiproliferative activity towards human cancer cell lines with MG_MID GI50 values of 1.43 and 1.83 µM, respectively. Preliminary investigation revealed that compounds 15 and 23 might bind with ct-DNA through the intercalation mode which is responsible for potent bioactivity. Moreover, transportation behaviour indicated that these molecules could efficiently bind to and be carried by bovine albumin, and the hydrogen bonding and hydrophobic interactions played important roles in interaction with serum albumin.

Synthesis of 5-(4-(1H-phenanthro[9,10-d]imidazol-2-yl)benzylidene)thiazolidine-2,4-dione as promising DNA and serum albumin-binding agents and evaluation of antitumor activity.

A series of phenanthro[9,10-d]imidazole/oxazole and acenaphtho[1,2-d]imidazole with different aryl groups at C2-position has been synthesized. These compounds were in vitro evaluated for antitumor activity against a panel of 60 human cancer cell lines. Compound 8 exhibits higher cytotoxicity towards leukemia, colon, melanoma, renal, and breast cancer cell lines than the other evaluated cell panels and low toxicity against normal cell line Hek293. The binding properties of compound 8 with DNA have been investigated with absorption, emission and circular dichroism as well as thermal denaturation experiments which indicate intercalation with base pairs of human and calf thymus DNA. The molecular docking and site-selective binding studies also reveal the predominant intercalation of compound 8 in base pairs of DNA. The interaction between thiazolidine based phenanthrene 8 and serum albumins (HSA and BSA), transport proteins, has also been explored which shows quenching of fluorescence through static mechanism. The thermodynamic parameters, obtained from van't Hoff relationship indicate the prevalence of hydrogen-bonding/hydrophobic interactions for the binding phenomenon.

Recent Advances and Developments of in†vitro Evaluation of Heterocyclic Moieties on Cancer Cell Lines.

Besides worthy development in cancer therapy, cancer is still one of the leading causes of death, worldwide. The future burden of cancer will probably be even larger because people are adopting poor lifestyles with poor diet, frequently smoking and less physical activity. The effective anticancer drugs having efficacy and selectivity with low toxicity is still a challenge for the scientific fraternity. The advances in the cancer study have its origin on the availability of different types of experimental model systems that review the various forms of this disease. Cell lines emerge as a feasible alternative for anticancer activities, being at the same time easy to manipulate and molecularly characterize. Heterocycles are key structural components of many of the anti-cancer drugs available on the market today. Indeed, of the novel molecular anti-cancer agents approved by the FDA between 2010 and 2017, almost two-thirds contained heterocyclic rings within their structures. This review summarizes and provides updated literature on heterocyclic compounds using various cancer cell lines reported during the period of 2014-2017 together with the structure-activity relationships.