Current Review Research Articles

Biginelli Reaction: A Multi-Component Type of Reaction and Synthetic Advancement in the Synthesis of Bioactive Dihydropyrimidinone Derivatives

Background: In synthetic and medicinal chemistry, multi-component reactions (MCRs) are considered an essential tool in synthesizing bioactive heterocyclic scaffolds. These reactions have been strategically used in drug discovery and development because of ease and economy. Objective: The current manuscript aims to highlight the importance of the Biginelli reaction in the synthesis of diverse dihydropyrimidinones with medicinal applications. Methods: We searched various keywords, including “multicomponent reaction”, “Biginelli reaction” and “dihydropyrimidinone” on “PubMed, PubChem, and google scholar” and collected the relevant articles for including the current work. Results: Biginelli reaction involving ketoester, aldehyde, and urea is a high-yielding, atomeconomical, environmentally benign reaction for developing a library of new dihydropyrimidinones to drive the process of drug discovery. Several developments were achieved with modifications of synthetic techniques, including C-H activation, coupling, cycloaddition, etc. Inclusively, these modifications give access to a wide range of dihydropyrimidinones. Conclusion: The current review provides an overview of recent developments in the Biginelli reaction and insights into synthesizing bioactive dihydropyrimidinones.

Glp-1 Mimetics and Autophagy in Diabetic Milieu: State-of-the-Art.

The diabetic milieu is associated with cascades of pathophysiological pathways that culminate in diabetic complications and tissue injuries. Autophagy is an essential process mandatory for cell survival and tissue homeostasis by degrading damaged organelles and removing injured cells. However, it may turn into a pathological process in an aberrant mode in the diabetic and/or malignant milieu. Moreover, autophagy could serve as a promising therapeutic target for many complications related to tissue injury. Glp-1 mimetics are a class of newer antidiabetic agents that reduce blood glucose through several pathways. However, some evidence suggests that they can provide extra glycemic benefits by modulating autophagy, although there is no complete understanding of this mechanism and its underlying molecular pathways. Hence, in the current review, we aimed to provide new insights on the possible impact of Glp-1 mimetics on autophagy and consequent benefits as well as mediating pathways.

Natural Products as Inhibitors of Coronavirus: An Update

Abstract: In the past couple of decades, several corona virus infections have alarmed the world claiming deaths of huge population over the globe. Effective anti-viral agents have been researched for treatment of COVID-19 infection. Vaccination has come up as an ultimate prevention against SARS-CoV-2virus as many vaccines have been recommended by WHO to be used for prevention from COVID-19. Alternative treatment strategies to combat infection include drug repurposing as well as supportive therapies. Traditional medicines being used from ancient times for different disease conditions provide a wealth of chemical diversity. Different classes of natural products are being utilized to study their antiviral properties and contributed in past for different viral diseases. The aim of current review is to enumerate different secondary metabolites and their pharmacophoric features against corona viruses that can be further optimized to develop more potent inhibitors specific to SARS-CoV-2. This review systematically evaluates natural products and their synthetic/ semisynthetic analogs belonging to terpenoids, polyphenols, saponins, and alkaloids having antiviral activity against coronaviruses. The information obtained from scope of Indian medicinal plants is also discussed which may be evaluated in future against SARS-CoV-2. Thus, it is proposed that the natural products may be used to develop potential inhibitors using the knowledge gained from similar studies to prevent morbidity and mortalities due to SARS-CoV-2.

Pharmacological Activities of the Roots of Stemona tuberosa Medicinal Plant: An Overview

: Since childhood, plants and plant products have been used extensively as medicine. The majority of rural residents still rely on natural resources and the old-fashioned medical system for their daily needs. The biological richness of Arunachal Pradesh is renowned, as is its rich cultural diversity. The native population uses a number of aromatic and medicinal plant species to cure a wide range of illnesses. The current review deals with the biological activity of Stemona tuberosa, a possible medicinal plant species of Arunachal Pradesh. Extract from tuberous roots has numerous properties, including anti-bacterial, anti-inflammatory, anti-tobacco mosaic virus, antitussive, wound healing, and anti-herpes. The roots' powder is employed as a preservation and insect deterrent. Alkaloids, sugars and glycosides, phenolic compounds, trace amounts of proteins, saponin, flavonoids, and gum mucilage, were all found during the phytochemical analysis, which shows that the species has a significant potential for therapeutic use. As a result, it is possible to think of the examined species as a potential source of beneficial medications.

Recent Advancements in Bioelectronic Medicine: A Review.

Bioelectronic medicine is a multidisciplinary field that combines molecular medicine, neurology, engineering, and computer science to design devices for diagnosing and treating diseases. The advancements in bioelectronic medicine can improve the precision and personalization of illness treatment. Bioelectronic medicine can produce, suppress, and measure electrical activity in excitable tissue. Bioelectronic devices modify specific neural circuits using electrons rather than pharmaceuticals and uses of bioelectronic processes to regulate the biological processes underlining various diseases. This promotes the potential to address the underlying causes of illnesses, reduce adverse effects, and lower costs compared to conventional medication. The current review presents different important aspects of bioelectronic medicines with recent advancements. The area of bioelectronic medicine has a lot of potential for treating diseases, enabling non-invasive therapeutic intervention by regulating brain impulses. Bioelectronic medicine uses electricity to control biological processes, treat illnesses, or regain lost capability. These new classes of medicines are designed by the technological developments in the detection and regulation of electrical signaling methods in the nervous system. Peripheral nervous system regulates a wide range of processes in chronic diseases; it involves implanting small devices onto specific peripheral nerves, which read and regulate the brain signaling patterns to achieve therapeutic effects specific to the signal capacity of a particular organ. The potential for bioelectronic medicine field is vast, as it investigates for treatment of various diseases, including rheumatoid arthritis, diabetes, hypertension, paralysis, chronic illnesses, blindness, etc.

Nanostructured Lipid Carrier for Dermatological Application: A Comprehensive Review and Future Perspective

:Dermatological disease states have psychological impacts that affect a patient’s life. In the management of such disorders, topical delivery has an important role. However, the conven-tional topical delivery systems suffer from various limitations, like skin irritation, a minute quan-tity of drugs reaching disease sites, and over and under medication, which leads to an adverse re-action and therapeutic failure, respectively. Therefore, researchers continuously search for an al-ternate delivery system for treating skin disease. In recent years, nanostructured lipid carriers (NLC) have emanated as promising carrier systems for topical delivery. The current review pro-vides an in-depth insight into topical administration for treating a variety of dermatological issues using NLCs as a carrier. This review highlights the suitability of NLCs as carriers for topical de-livery, their method of preparation, and their characterization. In the present review, the main emphasis has been given to the management of various dermatological problems by using NLCs as a carrier; a plethora of literature investigating NLC as the carrier for topical delivery has been included in this review. In this paper, an attempt has been made to provide a summary of the re-search carried out in this field that will encourage further research in this arena.

Research Update on the Therapeutic Potential of Garden Cress (Lepidium sativum Linn.) with Threatened Status.

Garden cress (Lepidium sativum) has been used in India for medicinal purposes since the Vedic era. Garden cress, a native of Egypt and southwest Asia, is a small perennial edible herb that has been used to treat many diseases for centuries. The seeds, leaves as well as roots have medicinal properties. The seeds are rich in protein, fat, calcium, and iron and have high nutritional value. They are considered to be galactagogue, anticarcinogenic, antidiabetic, antiasthmatic and antidiarrheal. Leaves, seeds, and aerial parts extracts are found to have alkaloids, flavonoids, glycosides, polypeptides, vitamins, minerals, proteins, fats, and carbohydrates. Lepidium sativum is known for its pungent odor due to the several volatile oils and has been used to treat various conditions, including respiratory disorders, muscle pain, inflammation, and bone fractures in the past. Lepidium sativum is a fast-growing annual herb; in India, it is commonly known as Chandrasoor. Whole fruits or seeds are used, fresh or dried, as a seasoning with a peppery flavor. Boiled seeds are consumed in drinks by Arabs, either ground in honey or as an infusion in hot milk. The seed oil can be used for illumination and soap making. Additionally, limited awareness and conservation efforts have further contributed to its threatened status. Recognizing the importance of preserving this valuable plant species is crucial for maintaining biodiversity and ensuring its availability for future generations. Furthermore, this review explores the potential benefits of Lepidium sativum in different domains. Its nutritional value and health benefits make it a promising candidate for addressing malnutrition and improving overall well-being. The presence of bioactive compounds suggests its potential use in functional foods, pharmaceuticals, and natural medicines for various ailments. Moreover, Lepidium sativum exhibits antimicrobial and insecticidal properties, offering potential applications in agriculture and pest control. The current review discussed the nutritional, potential benefits and pharmacological effects of Lepidium sativum.

Pediatric Trauma - A Silent Epidemic.

Trauma is the leading cause of preventable deaths in children all over the world. In the majority of cases, children are innocent victims of road traffic accidents. They suffer from both short-term and long-term impacts of trauma. Deaths from road traffic accidents can be prevented by adopting simple road safety measures and the use of protective equipment. Worldwide programs have been initiated to curb this ever-rising menace; however, the success of these programs depends on their outreach and acceptance among the population in general. Golden hours in trauma management is the initial hour post-trauma, the success of resuscitation depends on the appropriate management of pediatric trauma victims in hospitals dedicated to the management of pediatric trauma victims. The current review highlights the epidemiology, pattern of injury, road safety measures, and global health initiatives for the prevention of accident-related injury in children. The shortcomings of this review are as follows- Firstly pediatric trauma is an exhaustive topic, it is impossible to cover all aspects of pediatric trauma. Thus, the review might have missed some important aspects of pediatric trauma. Secondly, the concept of a pediatric trauma registry is nonexistent in almost all developing countries; hence a true picture of pediatric trauma epidemiology and injury patterns is missing. Thirdly not much work has been done on pediatric trauma in developing countries leading to insufficient data from these countries.

Bioanalytical methods and extraction techniques for the quantification of hydrochlorothiazide and its pharmaceutical combinations: A comprehensive review

AbstractHydrochlorothiazide has been utilized clinically for the past half-century, which is popularly known as a “water pill” as it produces increased urine output. The advancement of bioanalytical methods brought a dynamic field with exciting opportunities for future research. The current review emphasis the bioanalytical methods employed for the quantitative estimation of Hydrochlorothiazide as monotherapy and its popularly used combinational medications available from 1956 to till date. A fixed dose of 25 mg of hydrochlorothiazide with 43 combinational medications is currently available in the market and these combinations are widely employed in the treatment of hypertensive people; those whose blood pressure does not respond effectively to monotherapy of hydrochlorothiazide and also for the treatment of edema (excess fluid in the body) caused by illness such as heart failure, liver problems, and renal disease. It has been convincingly demonstrated that the combination of any two antihypertensive medications belonging to different groups of the same category, significantly lowers blood pressure, in comparison with the effect produced by increasing the dose of a single medicament. Among the various analytical techniques employed for the estimation of Hydrochlorothiazide, the review portrays that hyphenated technique, in specific liquid chromatography coupled with mass spectroscopy was widely employed. The validation parameters namely linearity, LOD, LOQ for individual drug and their combinations, were successfully calibrated. The effectiveness of analytical approaches was evaluated and enhanced for chemical factors. The involvement of green chemistry in the optimized methods for the evaluation of Hydrochlorothiazide for the future development, are suggested.

Herbs for the Therapy of Diabetes Mellitus: A Thorough Analysis with Particular Emphasis on Preclinical, Clinical Trials, and their Hypothesised Mechanisms

Background: In recent times, herbal medicines have experienced an expansion in both developing and developed countries due to their natural origin and low incidence of adverse effects. A systematic review was performed to gather information regarding herbal plants used to treat diabetes mellitus. Objective: The aim of this article was to review evidence from preclinical and clinical trials and the proposed mechanism of herbal drugs in diabetes mellitus. Methods: A literature survey was carried out mainly focused on scientific papers published in recent years. The search strategy involved interrelated keywords, like “Diabetes mellitus,” “Herbs,” “Hyperglycaemia,” and other uniterms. Electronic databases used were Scopus, Web of Science, PubMed, and Elsevier. Results: Twenty studies, including preclinical and clinical trials, were selected for evaluating the mechanism of the anti-hyperglycaemic effect of herbal drugs in diabetes mellitus. Conclusion: Through clinical and preclinical research as well as an analysis of the mechanism of action of herbs, the current review provides preliminary evidence for possible anti-diabetic benefits of herbal medicines.

Natural Alkaloids and Mechanisms for Anti-cancer Action: A Review

: Cancer is a global public health issue. Cancer therapy has been hampered by the issue of multidrug resistance, which is one of the leading causes of death worldwide. As a result, the use of natural derived drugs for cancer prevention and therapy has been researched and developed for decades. Alkaloids are plant-derived secondary metabolites that have antiproliferative and anticancer effects on several forms of cancer. Camptothecin and vinblastine, two anticancer medicines derived from alkaloids, have been adequately developed in the past. Alkaloids, a drug lead compounds, derived from natural products, have the advantage of being used by the host, making them suitable for further exploitation. The current review looks at the anticancer potential of numerous naturally occurring alkaloids, as well as the mechanism behind their anticancer effect.

Promising Influences of Moringa oleifera in Functional Foods against Metabolic Syndrome: A Comprehensive and Mechanistic Review.

Metabolic syndrome (MetS) is now considered a global issue with a growing financial and health impact. Numerous herbal alternatives have been examined and researched due to the ever-increasing demand for new medications to treat metabolic syndrome disorders. People have empirically employed Moringa oleifera (MO), a native plant to several Asian nations, for a variety of diseases. We sought to examine recent research on MO in MetS and its potential mechanism of action in the current review. Four databases, including PubMed, Scopus, Web of Sciences, and Google Scholar, were thoroughly searched, and the data were then compiled. In total, 146 papers covering nonclinical and clinical MO investigations in metabolic syndromerelated disorders are included in this study. Numerous research confirmed MO's positive impact on the control of blood glucose, blood pressure, hyperlipidemia, and obesity. Many molecular processes have been investigated, including increasing glucose transporter type 4 (GLUT4) expression, inhibition of β-Hydroxy-β-methylglutaryl-coenzyme A (HMG-CoA), α-glucosidase inhibiting, AMP-activated protein kinase (AMPK) activation, and other suggested mechanisms. The current review established much data favoring MO's potential advantages in metabolic syndrome. However, further research involving human studies is required in this area to determine whether Moringa can effectively treat metabolic syndrome.

Epigrammatic Review on Heterocyclic Moiety Pyrazole: Applications and Synthesis Routes

Abstract: Heterocyclic compounds are amongst the most promising and versatile classes of biologically important molecules. One of the heterocycle molecules is pyrazole with a five-membered heterocyclic ring with two neighboring nitrogen. Pyrazole and its derivatives have shown a broad range of biological applications like antibacterial, antifungal, antiviral, anti-inflammatory, anti-cancerous, and herbicidal activities. The study of synthetic routes suggests three broad ways: cyclo-condensation of hydrazine and its derivatives on 1,3 difunctional systems, dipolar cycloadditions, and multicomponent reactions. The synthesis of pyrazoles involves the usage of a conventional catalyst and more progressive and efficient nanoparticles as catalysts. The use of nanocatalysts is grabbing the attention of researchers owing to their more efficacy and reproducibility, low cost, reusability, ease of production, etc. The current review is an epigrammatic study on the importance of pyrazole as a biologically important moiety, recent advances in the three aforementioned routes to synthesize pyrazole and its derivatives, and a brief on the importance of nanocatalysts.

Recent advancements in novel formulations of anti-psoriatic agents for effective delivery: clinical importance and patent survey.

Objectives An autoimmune-mediated dermatological ailment featuring recurrent episodes is acknowledged as psoriasis. Around the world, 2-3% of people suffer from this autoimmune skin condition. The primary goal of the current review is to analyse and determine the effectiveness of conventional and emerging nano technological strategies to alleviate psoriasis and discuss future perspectives. Evidence acquisition A thorough search of numerous electronic databases, including Science Direct, Scopus, Google Scholar, Clinical Trials, Google Patents, Research Gate, and PubMed, yielded all the data used in this review paper about the management of psoriasis via various anti-psoriatic agent and nanotechnology approaches. Keywords such as topical, liposomes, niosomes, micro needles, clinical trials, patents, pathogenesis, biosimilars, cytokines, and other pertinent words were investigated. Results Nano technological approaches are gaining prominence since they enable targeted delivery, rapid onset of action with limited systemic exposure. Researchers have investigated innovative, alternative therapeutic approaches that are both secure and efficient for treating psoriatic conditions. Further, the potential role of numerous psoriatic conventional therapies has been explored. The patents granted or in process to address psoriasis via topical route have been well explored. Modern nanotechnology has made it possible for pharmaceuticals to be delivered with improved physical, chemical, pharmacokinetic, and pharmacodynamic qualities. Despite extensive research complete cure for psoriasis is hampered. Conclusion Relying on the extensive literature review, it can be inferred that nanoparticles based novel delivery strategies have the possibility of enhancing the pharmacological activity and eliminating or resolving problems associated with this ailment. The different drug delivery systems available for the treatment of psoriasis along with the clinical trials in different stages, patents in process and granted, the commercialized status of therapeutic molecules, and the future of research in this area have been thoroughly reviewed.

Redox imbalance and metabolic defects in the context of Alzheimer disease.

Redox reactions play a critical role for intracellular processes, including pathways involved in metabolism and signaling. Reactive oxygen species (ROS) act either as second messengers or generators of protein modifications, fundamental mechanisms for signal transduction. Disturbance of redox homeostasis is associated with many disorders. Among these, Alzheimer's disease is a neurodegenerative pathology that presents hallmarks of oxidative damage such as increased ROS production, decreased activity of antioxidant enzymes, oxidative modifications of macromolecules, and changes in mitochondrial homeostasis. Interestingly, alteration of redox homeostasis is closely associated with defects of energy metabolism, involving both carbohydrates and lipids, the major energy fuels for the cell. As the brain relies exclusively on glucose metabolism, defects of glucose utilization represent a harmful event for the brain. During aging, a progressive perturbation of energy metabolism occurs resulting in brain hypometabolism. This condition contributes to increase neuronal cell vulnerability ultimately resulting in cognitive impairment. The current review discusses the crosstalk between alteration of redox homeostasis and brain energy defects that seems to act in concert in promoting Alzheimer's neurodegeneration.

Impact of Mesenchymal Stem Cells on the Gut Microbiota and Microbiota Associated Functions in Inflammatory Bowel Disease: A Systematic Review of Preclinical Evidence on Animal Models.

Inflammatory bowel disease (IBD) is a global health problem in which gut microbiota dysbiosis plays a pivotal pathogenic role. Mesenchymal stem cells (MSCs) therapy has shown promising application prospects for its powerful immune regulation and tissue repair ability. Recent experimental data suggest that MSCs also regulate the composition of gut microbiota. The current review analyzed, for the first time, the research data linking MSCs and gut microbiota modulation in IBD models aiming at assessing the role of gut microbiota in MSCs repair of IBD. A comprehensive and structured literature search was performed up to January 2023 on the PubMed, Web of Science, and Scopus databases. The quality and risk of bias assessment followed the PRISMA guidelines and SYRCLE's tool. A total of nine pre-clinical studies on animal models were included. Although the dose and route of MSCs applied were quite heterogeneous, results showed that MSCs displayed protective effects on intestinal inflammation, including mice general assessment, immunoregulation, and intestinal barrier integrity. Meanwhile, studies showed positive effects on the composition of gut flora with MSCs administration, which had been characterized by restoration of Firmicutes/ Bacteroides balance and reduction of Proteobacteria. The beneficial bacteria Akkermansia, Bifidobacterium, and Lactobacillus were also distinctly enriched, and the pathogenic bacteria Escherichia-Shigella was conversely decreased. The alpha and beta diversity were also regulated to resemble those of healthy mice. Microbial metabolic functions, such as biosynthesis of secondary bile acid and sphingolipid metabolism, and some biological behaviors related to cell regeneration were also up-regulated, while cancer function and poorly characterized cellular function were down-regulated. Current data support the remodeling effect on gut microbiota with MSC administration, which provides a potential therapeutic mechanism for MSCs in the treatment of IBD. Additional studies in humans and animal models are warranted to further confirm the role of gut microflora in MSCs repairing IBD.

Hydrogel-based Drug Delivery System in Diabetes Management.

It is estimated that there are over 200 million people living with diabetes mellitus (DM) all over the world. It is a metabolic condition caused by decreased insulin action or secretion. Diabetes Mellitus is also known as Type 2 Diabetes Mellitus. Type 1 diabetes mellitus and type 2 diabetes mellitus are the two most common types of DM. Treatment for type 1 diabetes often consists of insulin replacement therapy, while treatment for type 2 diabetes typically consists of oral hypoglycemics. Conventional dosing schedules for the vast majority of these medications come with a number of drawbacks, the most common of which are frequent dosing, a short half-life, and low bioavailability. Thus, innovative and regulated oral hypoglycemic medication delivery methods have been developed to reduce the limitations of standard dose forms. The studies and reviews published under the title were looked up in several databases (including PubMed, Elsevier, and Google Scholar). Hydrogels made from biopolymers are three-dimensional polymeric networks that can be physically or chemically crosslinked. These networks are based on natural polymers and have an inherent hydrophilic quality because of the functional groups they contain. They have a very high affinity for biological fluids in addition to a high water content, softness, flexibility, permeability, and biocompatibility. The fact that these features are similar to those of a wide variety of soft living tissues paves the way for several potentials in the field of biomedicine. In this sense, hydrogels offer excellent platforms for the transport of medications and the controlled release of those drugs. Additionally, biopolymer-based hydrogels can be put as coatings on medical implants in order to improve the biocompatibility of the implants and to prevent medical diseases. The current review focuses on the most recent advancements made in the field of using biopolymeric hydrogels that are physically and chemically crosslinked, in addition to hydrogel coatings, for the purpose of providing sustained drug release of oral hypoglycemics and avoiding problems that are associated with the traditional dosage forms of oral hypoglycemics.

Deciphering the Role of Peroxisome Proliferator-activated Receptor α and Phosphodiesterase Type 5 Targets in Alzheimer's Disease.

The most prevalent cause of dementia is Alzheimer's disease (AD). Although the global AD rate is on a constant rise, medical research is yet to find a cure for this neurological condition. Current available therapeutic drugs for AD treatment only provide symptomatic alleviation. Therefore, it is essential to establish effective AD treatment strategies in addressing clinical needs. The development of disease-modifying treatments for use in the disease's early stages and the advancement of symptomatic drugs principally used in the disease's later stages are priorities in AD research. Given that the etiology of AD is difficult to comprehend, using a multimodal therapy intervention that targets molecular targets of AD-related degenerative processes is a practical strategy to change the course of AD progression. The current review article discussed PPAR-α (Peroxisome proliferator-activated receptor-α) and PDE5 (Phosphodiesterase type 5) targets with evidence for their preclinical and clinical importance. Furthermore, we support the targets with AD-related processes, functions, and remedial measures. A unique synergistic method for treating AD may involve the beneficial combinatorial targeting of these two receptors. Furthermore, we reviewed different PDE chemical families in this research and identified PDE5 inhibitors as one of the promising AD-related experimental and clinical disease-modifying medications. Lastly, we suggest jointly targeting these two pathways would be more beneficial than monotherapy in AD treatments.

A Concise Review on Therapeutic Potential, Phytochemistry and Traditional Applications of Safed Musli (Chlorophytum borivilianum)

Background: In traditional medicine, Safed musli is a very popular herb. Natural sex tonics like Chlorophytum borivilianum (C. borivilianum) are effective in alleviating sexual disorders. Local healers in indigenous communities of India mostly use it for ethnic medicine. The circulation of blood is one of the functions it improves to enhance strength and energy. Since ancient times, the tuber roots of the plant Safed musli have been used to treat weakness and male impotency. Objective: The aim of this work is to bridge the scientific evidence with the pharmacological, phytochemical, and folkloric claims reported in different sources belonging to C. borivilianum. Methods: To build the manuscript, a detailed literature review was carried out by thoroughly analyzing globally accepted scientific research databases. Results: Safed musli is widely recognized for its efficacy in addressing male impotence. The abundant presence of phytoconstituents, particularly saponins, contributes to the nutritional and multifaceted therapeutic significance of C. borivilianum. Conclusion: The current review enlightens the pharmacotherapeutic potential of C. borivilianum, comprising its origin and distribution, botany, proximate composition, method of enhancing seed germination, pathology, phytochemistry, pharmacology, and traditional uses. The scope for future research is provided by the present review, which also furnishes a gateway for filling the existing gap in its various aspects of investigation.

Performance of Green Desymmetrization Methods toward Bioactive Cephalostatin Analogues.

Since the discovery of cephalostatins, which have shown remarkable activity against human cancer cells, they have attracted the attention of researchers to target the synthesis of such impressive, complicated molecules using the green desymmetrization approach. In the current review, we report the progress in the desymmetrization of symmetrical bis-steroidal pyrazines (BSPs) as an approach toward potentially active anti-- cancer agents, namely cephalostatins/ ritterazines. The achievement of synthesizing a gram-scaled prodrug with comparable activity to the potent natural cephalostatins using green methods is our primary target. These synthetic methods can be scaled up based on the symmetrical coupling (SC) of two steroidal units of the same type. Our secondary target is the discovery of new green pathways that help in structural reconstruction programming toward the total synthesis of at least one potentially active family member. The strategy is based on functional group interconversions with high flexibility and brevity using green selective methods. The introduction of controlling groups using nontrivial reconstruction methodologies forms the backbone of our work. After certain modifications to the symmetrical BSP starting material, the resulting analogs underwent several chemoselective transformations through three main routes in rings F, D, and C. One of these routes is the chemoselective spiroketal opening (ring-F). The second route was the functionalization of the Δ14,15 bond (ring-D), including chlorination/dechlorination, in addition to epoxidation/ oxygenation processes. Finally, the introduction of the C-11 methoxy group as a directing group on ring-C led to several chemoselective transformations. Moreover, certain transformations on C-12 (ring-C), such as methylenation, followed by hydroboration- oxidation, led to a potentially active analog. The alignment of these results directs us toward the targets. Our efforts culminated in preparing effective anti-cancer prodrugs (8, 24, 30, and 31), which are able to overcome cancer drug resistance (chemoresistance) by inducing the atypical endoplasmic reticulum-mediated apoptosis pathway, which works through the release of Smac/Diablo and the activation of caspase-4.