A Comprehensive Review on Nanoparticles as a Targeted Delivery System for the Treatment of Lung Cancer.

The second most common type of cancer is lung cancer, impacting the human population. Lung cancer is treated with a number of surgical and non-surgical therapies, including radiation, chemotherapy, and photodynamic treatment. However, the bulk of these procedures are costly, difficult, and hostile to patients. Chemotherapy is distinguished by inadequate tumour targeting, low drug solubility, and insufficient drug transport to the tumour site. In order to deal with the issues related to chemotherapy, extensive efforts are underway to develop and investigate various types of nanoparticles, both organic and inorganic, for the treatment of lung cancer. The subject of this review is the advancements in research pertaining to active targeted lung cancer nano-drug delivery systems treatment, with a specific emphasis on receptors or targets. The findings of this study are expected to assist biomedical researchers in utilizing nanoparticles (NPs) as innovative tools for lung cancer treatment, offering new methods for delivering drugs and reliable solid ligands.

Structural Perspective of Benzophenones Targeting Tubulin as Anticancer Agents.

Cancer is the leading cause of death and the most significant determinant of life expectancy in almost every country in this twenty-first century. According to the World Health Organization (WHO), cancer is responsible for the leading cause of death globally. Benzophenone derivatives are found in a variety of naturally occurring compounds which are known to be pharmacologically efficacious against a variety of diseases, including cancer. Microtubules are thought to be a good target for cancer chemotherapies. Microtubule polymerization and depolymerization are induced by a variety of natural, synthetic, and semisynthetic chemicals having a benzophenone nucleus, affecting tubulin dynamics. Several medications that affect microtubule dynamics are in various stages of clinical trials, including Combretastatins (phase II), Vincristine (clinically approved), Paclitaxel (in clinical usage), and epothilone (phase III), and only a few have been patented. Benzophenone derivatives target the colchicine binding site of microtubules, damage them and cause cell cycle arrest in the G2-M phase. Belonging to this class of molecules, phenstatin, a potent inhibitor of tubulin polymerization, has shown strongly inhibit cancer cell growth and arrest the G2/M phase of the cell cycle by targeting the colchicine binding site of microtubules. In the present manuscript, we described the benzophenone as tubulin polymerization inhibitors, their Structure-Activity Relationships (SARs) and molecular docking studies that reveal its binding affinity with the colchicine binding site.

Multiple Protein Biomarkers and Different Treatment Strategies for Colorectal Carcinoma: A Comprehensive Prospective.

In this review, we emphasized important biomarkers, pathogenesis, and newly developed therapeutic approaches in the treatment of colorectal cancer (CRC). This includes a complete description of small-molecule inhibitors, phytopharmaceuticals with antiproliferative potential, monoclonal antibodies for targeted therapy, vaccinations as immunotherapeutic agents, and many innovative strategies to intervene in the interaction of oncogenic proteins. Many factors combine to determine the clinical behavior of colorectal cancer and it is still difficult to comprehend the molecular causes of a person's vulnerability to CRC. It is also challenging to identify the causes of the tumor's onset, progression, and responsiveness or resistance to antitumor treatment. Current recommendations for targeted medications are being updated by guidelines throughout the world in light of the growing number of high-quality clinical studies. So, being concerned about the aforementioned aspects, we have tried to present a summarized pathogenic view, including a brief description of biomarkers and an update of compounds with their underlying mechanisms that are currently under various stages of clinical testing. This will help to identify gaps or shortfalls that can be addressed in upcoming colorectal cancer research.

Curcumin and its Derivatives Targeting Multiple Signaling Pathways to Elicit Anticancer Activity: A Comprehensive Perspective.

The uncontrolled growth and spread of aberrant cells characterize the group of disorders known as cancer. According to GLOBOCAN 2022 analysis of cancer patients in either developed countries or developing countries the main concern cancers are breast cancer, lung cancer, and liver cancer which may rise eventually. Natural substances with dietary origins have gained interest for their low toxicity, anti-inflammatory, and antioxidant effects. The evaluation of dietary natural products as chemopreventive and therapeutic agents, the identification, characterization, and synthesis of their active components, as well as the enhancement of their delivery and bioavailability, have all received significant attention. Thus, the treatment strategy for concerning cancers must be significantly evaluated and may include the use of phytochemicals in daily lifestyle. In the present perspective, we discussed one of the potent phytochemicals, that has been used over the past few decades known as curcumin as a panacea drug of the "Cure-all" therapy concept. In our review firstly we included exhausted data from in-vivo and in-vitro studies on breast cancer, lung cancer, and liver cancer which act through various cancer-targeting pathways at the molecular level. Now, the second is the active constituent of turmeric known as curcumin and its derivatives are enlisted with their targeted protein in the molecular docking studies, which help the researchers design and synthesize new curcumin derivatives with respective implicated molecular and cellular activity. However, curcumin and its substituted derivatives still need to be investigated with unknown targeting mechanism studies in depth.

Structural Insights into N-heterocyclic Moieties as an Anticancer Agent against Hepatocellular Carcinoma: An Exhaustive Perspective.

Hepatocellular carcinoma (HCC) is rapidly spreading around the world with a high mortality rate. In the low- and middle-income nations most impacted by HCV and HBV infections, HCC places a significant strain on the healthcare system and leaches productive capability. An extensive study on HCC to create novel therapeutic approaches was motivated by the lack of adequate preventive or curative therapy methods. Several medications have been put forward and some drug molecules are under investigation by the Food and Drug Administration (FDA) for the treatment of HCC. However, these therapeutic choices fall short of the ideal due to toxicity and the rapid rise in drug resistance which decreases the efficacy of these therapeutics and leads to the severity of hepatocellular carcinoma. Therefore, concerning these problems, there is a critical need for novel systemic combination therapies as well as novel molecular entities that target various signalling pathways, reducing the likelihood that cancer cells may develop treatment resistance. In this review, we discuss the conclusions of several studies suggesting that the N-heterocyclic ring system is a key structural component of many synthetic drugs with a diverse range of biological activities. Following nuclei, such as pyridazine, pyridine, and pyrimidines, along with benzimidazole, indole, acridine, oxadiazole, imidazole, isoxazole, pyrazole, quinolines, and quinazolines, have been included to provide a general overview of the link between structure and activity between heterocyclics and their derivatives against hepatocellular carcinoma. A comprehensive investigation of the structure-activity relationship between the series may be done by the direct comparison of anticancer activities with the reference.

Computational approaches for the design of novel dopamine D2 and serotonin 5-HT2A receptor dual antagonist towards schizophrenia.

Piperidine and piperazine derivatives exhibit a diverse range of biological applications, including antipsychotic activity. In this study, a dataset of molecules containing piperidine, piperazine moieties that possess serotonin 5-HT2A and dopamine D2 inhibitory activity have been chosen for Pharmacophore modeling, Quantitative Structure-Activity (3D-QSAR) Relationship, Molecular docking, and ADME studies. The pharmacophoric hypothesis was found to be AAHPRRR_1 having seven features as one H-bond acceptor (A), one hydrophobic (H), one positive ion acceptor (P), and three aromatic rings (R), with survival score = 6.465 and AUC = 0.92. Based on the best hypothesis, the ZINC-Data base was virtually screened to find out the lead molecules. 3D-QSAR model, including internal and external validation showed comparative molecular field analysis (CoMFA) against 5HT2A (q 2 = 0.552, R 2 = 0.889, and r 2 poured. = 0.653 and number of component 5) and comparative molecular similarity indices analysis (CoMSIA) (q 2 = 0.599, R 2 = 0.893, and r 2 pred. = 0.617), for D2 (CoMFA, q 2 = 0.577, R 2 = 0.863, and r 2 pred. = 0.598) (CoMSIA, q 2 = 0.532, R 2 = 0.82) all results exhibited better productivity and significant statistical reliability of the model. The docking study was carried out on the crystal structure of 5-HT2A having PDB ID; 6A93 and D2 receptor having PDB ID; 6CM4. The screened compound ZINC74289318 possess a higher docking score - 10.744 and - 11.388 than co-crystallized ligand docking score - 8.840 and - 10.06 against 5-HT2A and D2 receptor respectively. Further, ZINC74289318 was screened for all drug-likeness parameters and no showed violation of the Lipinski rule of five. Also, it was found to possess good bioavailability of 0.55 with synthetic accessibility of 4.42 which is greater than risperidone.

Discovery of novel ALK2 inhibitors of pyrazolo-pyrimidines: A computational study.

ALK2 is a serine/threonine kinase, involved in different signaling pathways and associated with cell proliferation and differentiation. The present study includes development of pharmacophore, 3-D QSAR, docking and virtual screening studies on 30 different pyrazolo[1,5-a]pyrimidine derivatives. The pharmacophore study provides ARRR_2 hypothesis with four different features essential for ALK2 kinase inhibitory activity. The 3 D-QSAR study determined the statistically significant model by using partial least-square regression (PLS) method with R2 value of 0.9711 and Q2 value of 0.6846. Validation of 3 D-QSAR has been performed by LOO cross-validation method where with R2CV value of 0.56. The virtual screening study on ZINC database provides compounds such as ZINC66091638, ZINC43524105, ZINC19458227 and ZINC72441013 involved good binding interactions (docking scores -8.91, -7.40, -8.43, and -9.47, respectively) with ALK2 kinase (PDB ID: 3Q4U). The docking study of pyrazolo-pyrimidines derivatives found potent compounds, 7i, 13r, 13d, and 21 with docking scores -9.83, -9.75, -9.76, and -9.75, respectively. The important interactions with amino acid residues were HID 286, ASN341. ADME properties further assist to provide important structural features of ALK2 kinase. The present study may be help to medicinal scientists in the direction to develop potent inhibitors against ALK2 kinase.Communicated by Ramaswamy H. Sarma.

Recent advances in in silico design and characterization of superalkali-based materials and their potential applications: A review.

In the advancement of novel materials, chemistry plays a vital role in developing the realm where we survive. Superalkalis are a group of clusters/molecules having lower ionization potentials (IPs) than that of the cesium atom (3.89 eV) and thus, show excellent reducing properties. However, the chemical industry and material science both heavily rely on such reducing substances; an in silico approach-based design and characterization of superalkalis have been the focus of ongoing studies in this area along with their potential applications. However, although superalkalis have been substantially sophisticated materials over the past couple of decades, there is still room for enumeration of the recent progress going on in various interesting species using computational experiments. In this review, the recent developments in designing/modeling and characterization (theoretically) of a variety of superalkali-based materials have been summarized along with their potential applications. Theoretically acquired properties of some novel superalkali cations (Li3 +) and C6Li6 species, etc. for capturing and storing CO2/N2 molecules have been unveiled in this report. Additionally, this report unravels the first-order polarizability-based nonlinear optical (NLO) response features of numerous computationally designed novel superalkali-based materials, for instance, fullerene-like mixed-superalkali-doped B12N12 and B12P12 nanoclusters with good UV transparency and mixed-valent superalkali-based CaN3Ca (a high-sensitivity alkali-earth-based aromatic multi-state NLO molecular switch, and lead-founded halide perovskites designed by incorporating superalkalis, supersalts, and so on) which can indeed be used as a new kind of electronic nanodevice used in designing hi-tech NLO materials. Understanding the mere interactions of alkalides in the gas and liquid phases and the potential to influence how such systems can be extended and applied in the future are also highlighted in this survey. In addition to offering an overview of this research area, it is expected that this review will also provide new insights into the possibility of expanding both the experimental synthesis and the practical use of superalkalis and their related species. Superalkalis present the intriguing possibility of acting as cutting-edge construction blocks of nanomaterials with highly modifiable features that may be utilized for a wide-ranging prospective application.

Current Insights into the Chemistry and Antitubercular Potential of Benzimidazole and Imidazole Derivatives.

Tuberculosis is a disease caused by Mycobacterium tuberculosis (Mtb), affecting millions of people worldwide. The emergence of drug resistance is a major problem in the successful treatment of tuberculosis. Due to the commencement of MDR-TB (multi-drug resistance) and XDR-TB (extensively drug resistance), there is a crucial need for the development of novel anti-tubercular agents with improved characteristics such as low toxicity, enhanced inhibitory activity and short duration of treatment. In this direction, various heterocyclic compounds have been synthesized and screened against Mycobacterium tuberculosis. Among them, benzimidazole and imidazole containing derivatives have been found to have potential anti-tubercular activity. The present review focuses on various imidazole and benzimidazole derivatives (from 2015-2019) with their structure-activity relationships in the treatment of tuberculosis.

An exhaustive perspective on structural insights of SGLT2 inhibitors: A novel class of antidiabetic agent.

Diabetes mellitus is the global health issue and become an alarming threat in the modern era where human lifestyle gets compromised with modernization. According to the latest statistical report 2020, USA has 9.47% (31 million among 32.72 cr), China has 8.3% (116.4 million among 139.27 cr) and India has 5.6% (77 million among 135.26 cr) of the diabetic people, indicating that diabetes is more prevailing in developed countries as compared to the developing countries. The number of diabetic patients is rising day by day at a tremendous rate and soon it may affect each and every person in a family. So, there is an urgent need to develop novel entities that can meet the scarcity of present antidiabetic agents. In the last few decades, the sodium-glucose co-transporter 2 (SGLT2) has emerged as a prominent target for the treatment of Type 2 diabetes mellitus due to its novel mechanism of action & no involvement in insulin signaling pathway. Most of the inhibitors that target SGLT2 contain three basic moieties: glucose, two benzene rings (one is connected with glucose and the other with methylene), and the methylene bridge which are similar to dapagliflozin. Several SGLT2 inhibitors and their derivatives such as remogliflozin etabonate (phase-II), sotagliflozin (phase-III) and bexagliflozin (phase-III) are under different phases of clinical trial studies and some have been patented. The present review is focused on SGLT2 inhibitors, structure activity relationships (SARs) of dapagliflozin and its several analogues for their binding affinity with SGLT2. We have also presented and summarized the efforts made by various researchers in terms of the synthesis of various dapagliflozin derivatives till date.