The futuristic applications of transition metal dichalcogenides for cancer therapy.

The second-most common cause of death resulting from genetic mutations in DNA sequences is cancer. The difficulty in the field of anticancer research is the application of the traditional methods, which also affects normal cells. Mutations, genetic replication alterations, and chromosomal abnormalities have a direct impact on the effectiveness of anticancer drugs at different stages. Presently, therapeutic techniques utilize nanotechnology, transition metal dichalcogenides (TMDCs), and robotics. TMDCs are being increasingly employed in tumor therapy and biosensing applications due to their biocompatibility, adjustable bandgap, versatile functionality, exceptional photoelectric properties, and wide range of applications. This study reports the advancement of nanoplatforms based on TMDCs that are specifically engineered for responsive and intelligent cancer therapy. This article offers a thorough examination of the current challenges, future possibilities for theranostic applications using TMDCs, and recent progress in employing TMDCs for cancer therapy. Currently, there is significant interest in two-dimensional (2D) TMDCs nanomaterials as ultrathin unique physicochemical properties. These materials have attracted attention in various fields, including biomedicine. Due to their inherent ability to absorb near-infrared light and their exceptionally large surface area, significant efforts are being made to prepare multifunctional nanoplatforms based on 2D TMDCs.

Mechanism and potentialities of photothermal and photodynamic therapy of transition metal dichalcogenides (TMDCs) against cancer.

The ultimate goal of nanoparticle-based phototherapy is to suppress tumor growth. Photothermal therapy (PTT) and photothermal photodynamic therapy (PDT) are two types of physicochemical therapy that use light radiation with multiple wavelength ranges in the near-infrared to treat cancer. When a laser is pointed at tissue, photons are taken in the intercellular and intracellular regions, converting photon energy to heat. It has attracted much interest and research in recent years. The advent of transition materials dichalcogenides (TMDCs) is a revolutionary step in PDT/PTT-based cancer therapy. The TMDCs is a multilayer 2D nano-composite. TMDCs contain three atomic layers in which two chalcogens squash in the transition metal. The chalcogen atoms are highly reactive, and the surface characteristics of TMDCs help them to target deep cancer cells. They absorb Near Infrared (NIR), which kills deep cancer cells. In this review, we have discussed the history and mechanism of PDT/PTT and the use of TMDCs and nanoparticle-based systems, which have been practiced for theranostics purposes. We have also discussed PDT/PTT combined with immunotherapy, in which the cancer cell apoptosis is done by activating the immune cells, such as CD8+.

Anastomosing haemangioma of adrenal gland: an unusual vascular tumour.

With only 15 reported cases, anastomosing haemangioma of adrenal is a rare entity and usually presents as adrenal incidentaloma. A hypertensive, diabetic, non-smoker man in his late 60s presented with irritative voiding symptoms. On evaluation, he was found to have a urinary bladder mass and left adrenal incidentaloma measuring 8 cm. Metabolic evaluation confirmed it to be non-functional.The patient underwent transurethral resection of bladder tumour with left laparoscopic adrenalectomy. Intraoperatively, the adrenal tumour was highly vascular with multiple feeder vessels. Grossly it was soft, encapsulated with focal grey-brown areas. Microscopically, most of adrenal gland was replaced by anastomosing proliferating capillary vessels within framework of non-endothelial supporting cells reminiscent of splenic sinusoids. The tumour was positive for CD-31, CD-34, Glut-1 and SMA.Anastomosing haemangioma is a benign entity but it must be differentiated from angiosarcoma. Characteristic imaging features are not yet defined and is, therefore, difficult to diagnose preoperatively.

Synthesis, molecular docking and biological evaluation of 1,2,4-oxadiazole based novel non-steroidal derivatives against prostate cancer.

Prostate cancer is one of the most prevalent cancers in men leading to second most death causing cancer in men. Despite the availability of multiple treatment still the prevalence is high for prostate cancer. Steroidal antagonists associated with poor bioavailability, side effects while non-steroidal antagonists show serious side effects like gynecomastia. Therefore, there is a need of potential candidate for the treatment of prostate cancer with better bioavailability, good therapeutic effect and minimal side effects. In the same context, we have designed the series, SP1-SP25 based 3-phenyl-5-styryl-1,2,4-oxadiazole as the core structure. We successfully synthesized all 25 molecules in this series and characterized them using 1H, 13C NMR, and mass spectroscopy. Subsequently, we conducted MTT assays using PC-3 cells and observed that all the compounds exhibited a dose-dependent decrease in cell viability. Notably, compounds SP04, SP16, and SP19 demonstrated a significant decrease in cell viability and exhibited potent activity compared to the other synthesized molecules and standard drug bicalutamide. Among them, SP04 emerged as the one of the most potent compounds with an IC50 value of 238.13 nM and an 89.99 % inhibition of PC-3 cells, compared to synthesized molecules and standard drug bicalutamide. Furthermore, we conducted ROS assays and androgen receptor inhibition assays using the potent compound SP04 and bicalutamide. The results indicated that SP04 increased ROS production and decreased androgen receptor expression dose-dependent manner. Additionally, we conducted a docking study to analyse the interaction patterns within the active site of the androgen receptor. ADMET analysis revealed that all the compounds exhibited favorable physicochemical properties and manageable toxicity profiles.

Therapeutic charisma of imidazo [2,1-b] [1,3,4]-thiadiazole analogues: a patent review.

Imidazothiadiazole was discovered around the 1950s era, containing an imidazole ring fused to a thiadiazole ring. Imidazothiadiazole exhibit versatile pharmacological properties including anticonvulsant, cardiotonic, anti-inflammatory, diuretic, antifungal, antibacterial and anticancer. Despite of the being discovered in 1950s, the imidazothiadiazole derivatives are unable to being processed to clinical trials because of lack of bioavailability, efficacy and cytotoxicity. The recent patent literature focused on structural modification of imidazothiadiazole core to overcome these problems. This review limelight a disease-centric perspective on patented imidazothiadiazole from 2015-2023 and to understand their mechanism of action in related diseases. The relevant granted patent applications were located using patent databases, Google Patents, USPTO, EPO, WIPO, Espacenet and Lens.

A Rationalized Approach to Design and Discover Novel Non-steroidal Derivatives through Computational Aid for the Treatment of Prostate Cancer.

BACKGROUND: Prostate cancer is one of the most prevalent cancers in men, leading to the second most common cause of death in men. Despite the availability of multiple treatments, the prevalence of prostate cancer remains high. Steroidal antagonists are associated with poor bioavailability and side effects, while non-steroidal antagonists show serious side effects, such as gynecomastia. Therefore, there is a need for a potential candidate for the treatment of prostate cancer with better bioavailability, good therapeutic effects, and minimal side effects. OBJECTIVE: This current research work focused on identifying a novel non-steroidal androgen receptor antagonist through computational tools, such as docking and in silico ADMET analysis. METHODS: Molecules were designed based on a literature survey, followed by molecular docking of all designed compounds and ADMET analysis of the hit compounds. RESULTS: A library of 600 non-steroidal derivatives (cis and trans) was designed, and molecular docking was performed in the active site of the androgen receptor (PDBID: 1Z95) using AutoDock Vina 1.5.6. Docking studies resulted in 15 potent hits, which were then subjected to ADME analysis using SwissADME. ADME analysis predicted three compounds (SK-79, SK-109, and SK-169) with the best ADME profile and better bioavailability. Toxicity studies using Protox-II were performed on the three best compounds (SK-79, SK-109, and SK-169), which predicted ideal toxicity for these lead compounds. CONCLUSION: This research work will provide ample opportunities to explore medicinal and computational research areas. It will facilitate the development of novel androgen receptor antagonists in future experimental studies.

Recent advances of benzimidazole as anticancer agents.

Cancer is the second leading cause of death globally, with 9.6 million deaths yearly. As a life-threatening disease, it necessitates the emergence of new therapies. Resistance to current chemotherapies drives scientists to develop new medications that will eventually be accessible. Because heterocycles are so common in biological substances, compounds play a big part in the variety of medications that have been developed. The "Master Key" is the benzimidazole nucleus, which consists of a six-membered benzene ring fused with a five-membered imidazole/imidazoline ring, which is an azapyrrole. One of the five-membered aromatic nitrogen heterocycles identified in American therapies that have been approved by the Food and Drug Administration (FDA). Our results show that benzimidazole's broad therapeutic spectrum is due to its structural isosteres with purine, which improves hydrogen bonding, electrostatic interactions with topoisomerase complexes, intercalation with DNA, and other functions. It also enhances protein and nucleic acid inhibition, tubulin microtubule degeneration, apoptosis, DNA fragmentation, and other functions. Additionally, readers for designing the more recent benzimidazole analogues as prospective cancer treatments.

Role of Tyrosine Kinases and their Inhibitors in Cancer Therapy: A Comprehensive Review.

BACKGROUND: Cancer has been recognized as one of the non-communicable diseases with an increasing number of new cases, higher morbidity, and higher mortality rates at the global level. Thus, there is non-stop search for novel targets and small molecules to improve the chemotherapeutic outcomes concerning potency, selectivity, efficiency, affinity, ADMET, etc. Among anticancer therapeutic targets, tyrosine kinase has been documented well and approved as an important target with the development of various clinically used drugs. There are several structurally diverse small molecules in different preclinical and clinical stages of development that act by affecting tyrosine kinases in cancerous cells. Here, we have summarized different potent molecules acting against tyrosine kinases that can be considered as anticancer agents. OBJECTIVE: The current review focused on structural aspects of different chemical agents for inhibition of tyrosine kinases as anticancer agents. METHODS: The present study provides a summarized review of published information on tyrosine kinase inhibitors, their binding pattern, potencies, and structure-activity relationships. The review also highlighted the structural aspects of the interaction between inhibitors and amino acid residues of tyrosine kinases. Moreover, it also provided a summary of different types of cancers and the currently available options for treatment. RESULTS: Several studies are being conducted for the inhibition of different tyrosine kinases using small molecules for the treatment of cancer. Tyrosine kinases have been reported involving in routine cellular functions, growth, and division of cells through different pathways which depend on phosphorylation. The overexpression and uncontrolled activity of tyrosine kinases have been identified as an important feature of cancerous cells. Thus, various small molecules have been reported which inhibit tyrosine kinases to block the growth and division of cancer cells. Here, more than 30 highly potent inhibitors of tyrosine kinases are summarised, which consist of pyrimidine, pyrazole, triazine, quinazoline, quinoline, pyrazine, chromene, etc. rings as a basic skeleton with different substituents. CONCLUSION: Inhibition of tyrosine kinases by different small molecules is an approved strategy for the development of novel anticancer agents. Several published reports have mentioned the characteristics of the different binding sites and crucial residues in tyrosine kinases for the design of novel molecular inhibitors. However, selectivity is an important criterion for the development of chemotherapeutic agents due to the existence of approximately 30 families of tyrosine kinases.

A Review on Modern Approaches to Benzimidazole Synthesis.

Cancer is the second most source of cessation of life globally, with 9.6 million expirations at each stage around the globe. The resistance to the current chemotherapies urges researchers to develop new drugs to be available in the market. Among the wide range of drugs synthesized, heterocyclic compounds play a major role due to the abundance of heterocyclic rings in biological substances. In medicinal chemistry, benzimidazole is an important pharmacophore and a privileged structure. This bicyclic compound is made up of the fusion of a six-membered benzene ring and a five-membered imidazole ring with two nitrogen atoms at 1,3-positions. The benzimidazole ring has a great deal of stability. Many strong acids and alkalis do not affect benzimidazoles. The benzene ring of benzimidazole cleaves only under extreme conditions. Except in certain circumstances, the benzimidazole ring is also quite resistant to reduction. It is the most popular nucleus to study because of its wide range of biological functions. The recently developed methods for preparing benzimidazoles, such as condensation of o-phenylene diamines (OPDs) with aldehydes and many others using a wide range of nano, metal-based catalysts under solventfree conditions, are discussed in detail in the current studies.

Recent Developments in the Synthesis and Anticancer Activity of Indole and Its Derivatives.

Heterocyclic compounds are a class of compounds that is deeply intertwined with biological processes and is found in about 90% of commercially available medicines. They serve a critical function in medicinal chemistry and are focused in the field of medication development for their intensive research due to their broad variety of biological effects because of their intriguing molecular architecture, such as indoles are good candidates for drug development. It is a bicyclic structure consisting of a six-membered benzene ring fused to a five-membered pyrrole ring with several pharmacophores that yield a library of different lead compounds. Human cancer cells have been demonstrated to be inhibited by indoles in the development of new anticancer medicines. This is the first comprehensive review to focus on current methodologies for incorporating indole moiety, with their mechanistic targets as anticancer drugs, in order to shed light on the logical development of indole-based anticancer treatment options with high efficacy. This compiled data may serve as a benchmark for modifying existing ligands in order to design novel potent molecules through excellent yield synthesis techniques.

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.

Recurrent vesico-acetabulo-cutaneous fistula: lessons to be learnt.

A man in early 40s met with an accident with a complex pelvic fracture and extraperitoneal bladder injury and posterior urethral disruption 16 years ago. He additionally had left lumbar spinal segment mixed nerve injury, resulting in a foot drop. He underwent laparotomy and a diverting cystostomy at the time with a primary perineal urethroplasty a year later. He later developed pseudoarthrodesis of the hip joint, and poorly compliant bladder with complete block at bulbar urethra. A redo anastomotic urethroplasty was performed, hyperreflexive neurogenic bladder was managed with intravesical botox injections and underwent a hip replacement. Having defaulted botox injections, he developed a vesico-acetabulo-cutaneous fistula and the hip prosthesis was explanted. Later he underwent a ileal cystoplasty and a revision hip replacement. Ten years later, he presented with a recurrent fistula due to poor compliance with clean intermittent catheterisation. A challenging exploration with fistula excision was done with a primary bladder repair.

Tetrazole: A privileged scaffold for the discovery of anticancer agents.

Carcinoma, characterized by abnormal growth of cells and tissue, is a ubiquitously leading cause of mortality across the globe due to some carcinogenic factors. Currently, several anticancer agents are commercially available in the global market. However, due to their resistance and cost, researchers are gaining more interest in developing newer novel potential anticancer agents. In the search for new drugs for clinical use, the tetrazole ring system has emerged as an exciting prospect in the optimization studies of promising lead molecules. Among the various heterocyclic agents, tetrazole-containing compounds have shown significant promise in the treatment of a wide range of diseases, particularly cancer. Here, in this review, we focused on several synthetic approaches for the synthesis of tetrazole analogs, their targets for treating cancer along with the biological activity of some of the recently reported tetrazole-containing anticancer agents.

Glycogen Synthase Kinase 3 (GSK3): Its Role and Inhibitors.

Glycogen Synthase Kinase 3 (GSK3) is one of the Serine/Threonine protein kinases, which has gained a lot of attention for its role in a variety of pathways. It has two isoforms, GSK3α and GSK3ß. However, GSK3ß is highly expressed in different areas of the brain and has been implicated in Alzheimer's disease as it is involved in tau phosphorylation. Due to its high specificity concerning substrate recognition, GSK3 has been considered as an important target. In the last decade, several GSK3 inhibitors have been reported and two molecules are in clinical trials. This review collates the information published in the last decade about the role of GSK3 in Alzheimer's disease and progress in the development of its inhibitors. Using this collated information, medicinal chemists can strategize and design novel GSK3 inhibitors that could be useful in the treatment of Alzheimer's disease.

QSAR and Docking Studies of N-hydroxy Urea Derivatives as Flap Endonuclease-1 Inhibitors.

Flap endonuclease-I (FEN-1) is involved in DNA repair and considered to be a novel target for the development of anticancer agents. N-hydroxy urea derivatives have been reported as FEN-1 inhibitors. To derive in vitro and in silico correlation, we have performed 2D-quantitative structure activity relationship (QSAR) analysis and docking studies on these compounds. 2D-QSAR models were developed using multiple linear regression (MLR) analysis and cross-validation using leave one out (LOO) method. The best model displayed R(2) of 0.806 and Q(2) of 0.607. Docking study revealed key interactions with desired amino acids and compare well with the in vitro potency of the reported compounds. Both studies reveal a link between FEN-1 inhibition and physicochemical descriptors or interactions with amino acids in active site. The information generated is first of its kind and may be helpful in the design of novel FEN-1 inhibitors.

'Porcelain kidney': case report and review of the literature.

A rare case of pan-subepithelial dystrophic calcium deposition and bone marrow formation in hydronephrosis secondary to obstructive urolithiasis is reported and discussed. An elderly gentleman presented with accelerated hypertension, a nonfunctioning left kidney secondary to obstructive nephrolithiasis with additional pancalyceal calcification. His left retroperitoneoscopic nephrectomy specimen revealed sterile hydronephrosis secondary to an impacted ureteropelvic junction stone and pan-subepithelial fibrocalcific lamellar deposition. Special stains confirmed end-stage renal disease with chronic pyelonephritis with subepithelial dystrophic calcium deposition and evidence of bone marrow formation.

Differential expression of potassium ion channels in human renal cell carcinoma.

PURPOSE: Ether-a-go-go (EAG) or EAG-related (ERG) voltage-gated potassium ion channels are involved in tumor generation and progression. Their over- and/or misexpression has been demonstrated in various tumors, and inhibition of these channels has suppressed proliferation of various cancer cells. We investigate and compare the pattern of expression of EAG and human ERG (HERG) channels in renal cell carcinoma and "normal" renal tissue. METHOD: Tissue samples, obtained at the time of radical nephrectomy from the tumor-bearing areas, and uninvolved renal tissue were preserved in 4% paraformaldehyde and cryosectioned at 20 mum. Immunohistochemical and Western blot analysis was performed on the tumor and uninvolved kidney parenchyma by incubating with polyclonal anti-HERG 1b (Alomone Lab, Israel), anti-EAG1, and anti-EAG2. Pattern of expression of EAG/HERG channels in normal renal tissue and carcinoma were noted and compared. RESULTS: The study was performed on 16 radical and four partial nephrectomy specimens (n = 20). All tumors in the cohort were clear cell renal carcinoma. Normal renal tissue was found to exhibit heterogeneous cytoplasmic positivity for EAG1 and focal HERG immunoreactivity (IR) in the proximal (PCT) and distal convoluted tubules (DCT). EAG2 IR was absent in the normal renal tissue. Clear cell RCC demonstrated a loss of HERG expression while diffuse overexpression of EAG1 and EAG2 was noted. Western blot analysis corroborated the immunohistochemical observations. CONCLUSIONS: In our study both EAG1 and EAG2 potassium channels were overexpressed in clear cell renal cancer. In contrast to other adenocarcinomas, there is loss of HERG expression in clear cell RCC, which may possibly explain its chemoresistance. These ion channels may provide a potential for targeted therapy.

Robotic reconstruction for recurrent supratrigonal vesicovaginal fistulas.

PURPOSE: We report our experience with robotic reconstruction for recurrent supratrigonal vesicovaginal fistulas and its outcome. MATERIALS AND METHODS: From August 2006 to October 2007 we treated 7 cases of recurrent supratrigonal vesicovaginal fistula. Salient features of our technique are 1) vaginoscopy and cystoscopy with bilateral Double-J stent or ureteral catheter placement and placement of a catheter through the fistula from vagina to bladder, 2) patient positioning in a low lithotomy position with a 60-degree Trendelenburg tilt and a 5-port transperitoneal approach, 3) peritoneoscopy and adhesiolysis with minimal posterior cystotomy encircling the fistulous opening, 4) mobilization of the bladder and vaginal flaps to allow tension-free closure, 5) excision of the fistulous rim, 6) bladder and vaginal edge freshening, 7) bladder and vaginal closure, 8) omental, peritoneal or sigmoid epiploic tissue interposition and 9) insertion of a Foley catheter and drain. Difficulty was primarily noted with regard to the safe establishment of pneumoperitoneum, the need for extensive adhesiolysis, dissection of the fistula from perifistulous fibrosis in close vicinity to the ureteral opening, tension-free closure of the larger defect and occasional absence of omentum for use as interposition tissue. RESULTS: The average size of supratrigonal fistulas was 3.0 cm. Mean operative time was 141 minutes (range 110 to 160). Mean blood loss was 90 cc. No significant intraoperative or postoperative complications were observed. Mean hospital stay was 3 days. The catheter was removed 14 days postoperatively. All patients had a successful outcome. CONCLUSIONS: Our experience suggests that robotic repair for recurrent vesicovaginal fistulas is feasible, results in low morbidity and provides outstanding results. It provides an attractive option for vesicovaginal fistula repair by a minimally invasive approach for the surgeon and the patient alike.

Laparoscopic radical cystectomy and extracorporeal urinary diversion: a single center experience of 48 cases with three years of follow-up.

OBJECTIVES: To report our experience with laparoscopic radical cystectomy and extracorporeal urinary diversion for high-grade muscle invasive bladder cancer in a consecutive series of 48 patients with 3 years of follow-up. METHODS: From June 1999 to April 2006, 48 patients (42 men and 6 women; mean age 59 years, range 24 to 80) with bladder cancer underwent laparoscopic radical cystectomy and bilateral pelvic lymph node dissection at our institution. Urinary diversion was done extracorporeally through the specimen extraction incision. RESULTS: The mean operating time was 310 minutes, and the mean blood loss was 456 mL. In 1 patient, conversion to open surgery was required because of severe hypercarbia. Three major complications were observed intraoperatively (rectal injury in 2 and external iliac vein injury in 1 patient). However, all these complications were managed laparoscopically, with completion of the procedure laparoscopically. The mean hospital stay was 10.2 days (range 7 to 25). One patient died in the postoperative period of severe lower respiratory tract infection and septicemia. Histologic examination showed organ-confined tumors (Stage pT1/pT2/pT3a) in 34 patients (71%) and extravesical disease (pT3b/pT4) in 14 (29%). Of the 48 patients, 12 (25%) had lymph node involvement. The mean number of nodes removed was 14 (range 4 to 24). At a mean follow-up period of 38 months (range 10 to 72), 35 patients were alive with no evidence of disease (disease-free survival rate 73%). CONCLUSIONS: The results of our study have shown that laparoscopic radical cystectomy is a safe, feasible, and effective alternative to open radical cystectomy. Extracorporeal urinary diversion through a small incision decreases the operating time, while maintaining the benefits of laparoscopic surgery. The 3-year oncologic efficacy was comparable to that of open radical cystectomy.

First case series of robotic radical cystoprostatectomy, bilateral pelvic lymphadenectomy, and urinary diversion with the da Vinci S system.

One of the recent developments in the da Vinci robot surgical system is the introduction of a more ergonomic four-arm robot. We report our experience of robotic radical cystectomy (RRC) for bladder cancer using the four-arm da Vinci(®) S(TM) robot (Intuitive Surgical, Sunnyvale, CA, USA). Beginning September 2006, we performed robotic radical cystectomy and bilateral pelvic lymphadenectomy in six patients with muscle-invasive bladder cancer using da Vinci(®) S(TM) robot. Ileal conduit diversion was made in five patients, and sigmoid orthotopic neobladder in one patient. The operating surgeon used the fourth arm for various steps such as bladder retraction for defining vascular pedicles, separating cystoprostatectomy specimen off the rectum, and while performing urethroneovesicostomy. The mean operative time was 12, 148, 44, and 126 min for docking, cystectomy, lymphadenectomy, and urinary diversion, respectively. Median blood loss was 200 ml. Mean hospital stay was 9.2 days. Surgical margins were negative in all the patients. The mean number of nodes removed was 12 (4-19). Histopathology revealed transitional cell carcinoma in all the patients (pT2a-1, pT2b-3, pT3a-2). Robotic radical cystectomy is feasible with new four-arm da Vinci(®) S(TM) surgical system. The operating surgeon can use the fourth arm of the robot as a substitute for the second assistant during the procedure. However, a patient-side surgeon with adequate training in laparoscopic skills is mandatory.