Displaying publications 1 - 20 of 42 in total

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  1. Singh V, Shirbhate E, Kore R, Mishra A, Johariya V, Veerasamy R, et al.
    Mini Rev Med Chem, 2024 Feb 21.
    PMID: 38385496 DOI: 10.2174/0113895575283895240207065454
    Prostate cancer is a widespread malignancy among men, with a substantial global impact on morbidity and mortality. Despite advances in conventional therapies, the need for innovative and less toxic treatments remains a priority. Emerging evidence suggests that dietary plant metabolites possess epigenetic-modifying properties, making them attractive candidates for prostate cancer treatment. The present work reviews the epigenetic effects of dietary plant metabolites in the context of prostate cancer therapy. We first outline the key epigenetic mechanisms involved in prostate cancer pathogenesis, including histone modifications, DNA methylation, and miRNA or Long Noncoding RNA (lncRNA) dysregulation. Next, we delve into the vast array of dietary plant metabolites that have demonstrated promising anti-cancer effects through epigenetic regulation. Resveratrol, minerals, isothiocyanates, curcumin, tea polyphenols, soy isoflavones and phytoestrogens, garlic compounds, anthocyanins, lycopene, and indoles are among the most extensively studied compounds. These plant-derived bioactive compounds have been shown to influence DNA methylation patterns, histone modifications, and microRNA expression, thereby altering the gene expression allied with prostate cancer progression, cell proliferation, and apoptosis. We also explore preclinical and clinical studies investigating the efficacy of dietary plant metabolites as standalone treatments or in combination with traditional treatments for people with prostate cancer. The present work highlights the potential of dietary plant metabolites as epigenetic modulators to treat prostate cancer. Continued research in this field may pave the way for personalized and precision medicine approaches, moving us closer to the goal of improved prostate cancer management.
  2. Shirbhate E, Singh V, Mishra A, Jahoriya V, Veerasamy R, Tiwari AK, et al.
    Mini Rev Med Chem, 2024 Feb 09.
    PMID: 38343053 DOI: 10.2174/0113895575287242240129120002
    Chemotherapy is still the major method of treatment for many types of cancer. Curative cancer therapy is hampered significantly by medication resistance. Acidic organelles like lysosomes serve as protagonists in cellular digestion. Lysosomes, however, are gaining popularity due to their speeding involvement in cancer progression and resistance. For instance, weak chemotherapeutic drugs of basic nature permeate through the lysosomal membrane and are retained in lysosomes in their cationic state, while extracellular release of lysosomal enzymes induces cancer, cytosolic escape of lysosomal hydrolases causes apoptosis, and so on. Drug availability at the sites of action is decreased due to lysosomal drug sequestration, which also enhances cancer resistance. This review looks at lysosomal drug sequestration mechanisms and how they affect cancer treatment resistance. Using lysosomes as subcellular targets to combat drug resistance and reverse drug sequestration is another method for overcoming drug resistance that is covered in this article. The present review has identified lysosomal drug sequestration as one of the reasons behind chemoresistance. The article delves deeper into specific aspects of lysosomal sequestration, providing nuanced insights, critical evaluations, or novel interpretations of different approaches that target lysosomes to defect cancer.
  3. Patel V, Vaishnaw A, Shirbhate E, Kore R, Singh V, Veerasamy R, et al.
    Mini Rev Med Chem, 2023 Oct 10.
    PMID: 37861053 DOI: 10.2174/0113895575262104230928042150
    Cortisol, commonly known as the "stress hormone," plays a critical role in the body's response to stress. Elevated cortisol levels have been associated with various mental disorders, including anxiety, depression, and post-traumatic stress disorder. Consequently, researchers have explored cortisol modulation as a promising avenue for treating these conditions. However, the availability of research on cortisol as a therapeutic option for mental disorders is limited, and existing studies employ diverse methodologies and outcome measures. This review article aimed to provide insights into different treatment approaches, both pharmacological and non-pharmacological, which can effectively modulate cortisol levels. Pharmacological interventions involve the use of substances, such as somatostatin analogs, dopamine agonists, corticotropin-releasing hormone antagonists, and cortisol synthesis inhibitors. Additionally, non-pharmacological techniques, including cognitivebehavioral therapy, herbs and supplements, transcranial magnetic stimulation, lifestyle changes, and surgery, have been investigated to reduce cortisol levels. The emerging evidence suggests that cortisol modulation could be a promising treatment option for mental disorders. However, more research is needed to fully understand the effectiveness and safety of these therapies.
  4. Mourya A, Shubhra, Bajwa N, Baldi A, Singh KK, Pandey M, et al.
    Mini Rev Med Chem, 2023;23(9):992-1032.
    PMID: 35546778 DOI: 10.2174/1389557522666220511140527
    Osteoarthritis (OA), a chronic degenerative musculoskeletal disorder, progressively increases with age. It is characterized by progressive loss of hyaline cartilage followed by subchondral bone remodeling and inflammaging. To counteract the inflammation, synovium releases various inflammatory and immune mediators along with metabolic intermediates, which further worsens the condition. However, even after recognizing the key molecular and cellular factors involved in the progression of OA, only disease-modifying therapies are available such as oral and topical NSAIDs, opioids, SNRIs, etc., providing symptomatic treatment and functional improvement instead of suppressing OA progression. Long-term use of these therapies leads to various life-threatening complications. Interestingly, mother nature has numerous medicinal plants containing active phytochemicals that can act on various targets involved in the development and progression of OA. Phytochemicals have been used for millennia in traditional medicine and are promising alternatives to conventional drugs with a lower rate of adverse events and efficiency frequently comparable to synthetic molecules. Nevertheless, their mechanism of action in many cases is elusive and uncertain. Even though many in vitro and in vivo studies show promising results, clinical evidence is scarce. Studies suggest that the presence of carbonyl group in the 2nd position, chloro in the 6th and an electron- withdrawing group at the 7th position exhibit enhanced COX-2 inhibition activity in OA. On the other hand, the presence of a double bond at the C2-C3 position of C ring in flavonoids plays an important role in Nrf2 activation. Moreover, with the advancements in the understanding of OA progression, SARs (structure-activity relationships) of phytochemicals and integration with nanotechnology have provided great opportunities for developing phytopharmaceuticals. Therefore, in the present review, we have discussed various promising phytomolecules, SAR as well as their nano-based delivery systems for the treatment of OA to motivate the future investigation of phytochemical-based drug therapy.
  5. Dahiya S, Dahiya R, Fuloria NK, Mourya R, Dahiya S, Fuloria S, et al.
    Mini Rev Med Chem, 2022 Jan 13.
    PMID: 35049431 DOI: 10.2174/1389557522666220113122117
    Bridged peptide macrobicycles (BPMs) from natural resources belong to types of compounds that are not investigated fully in terms of their formation, pharmacological potential and stereo-chemical properties. This division of biologically active congeners with multiple circular rings, has merits over other varieties of peptide molecules. BPMs form one of the most hopeful grounds for establishment of drugs because of their close resemblance and biocompatibility to proteins, and these bio-actives are debated as feasible realistic tools in diverse biomedical applications. Despite huge potential, poor metabolic stability and cell permeability limit the therapeutic success of macrocyclic peptides. In this review, we have comprehensively explored major bicyclic peptides sourced from plants and mushrooms including βs-leucyl-tryptophano-histidine bridged and tryptophano-cysteine bridged peptide macrobicycles. The unique structural features, structure activity relationship, synthetic routes, bioproperties and therapeutic potential of the natural BPMs are also discussed.
  6. Khalifa M, Few LL, Too WCS
    Mini Rev Med Chem, 2021 Dec 13.
    PMID: 34961459 DOI: 10.2174/1389557521666211213160256
    BACKGROUND: Pseudomonas aeruginosa is one of the most prevalent opportunistic pathogens in humans that has thrived and proved to be difficult to control in this "post-antibiotic era." Antibiotic alternatives are necessary for fighting against this resilient bacterium. Even though phages might not be "the wonder drug" that solves everything, they still provide a viable option to combat P. aeruginosa and curb the threat it imposes.

    MAIN FINDINGS: The combination of antibiotics with phages, however, poses a propitious treatment option for P. aeruginosa. Choline kinase (ChoK) is the enzyme that synthesizes phosphorylcholine subsequently incorporated into lipopolysaccharide located at the outer membrane of gram-negative bacteria. Recently, inhibition of ChoKs has been proposed as a promising antibacterial strategy. Successful docking of Hemicholinium-3, a choline kinase inhibitor, to the model structure of P. aeruginosa ChoK also supports the use of this inhibitor or its derivatives to inhibit the growth of this microorganism.

    CONCLUSION: Therefore, the combination of the novel antimicrobial "choline kinase inhibitors (ChoKIs)" with a phage cocktail or synthetic phages as a potential treatment for P. aeruginosa infection has been proposed.

  7. Abbasi M, Yaqoob M, Haque RA, Iqbal MA
    Mini Rev Med Chem, 2021;21(1):69-78.
    PMID: 32767935 DOI: 10.2174/1389557520666200807130721
    Development of novel metallodrugs with pharmacological profile plays a significant role in modern medicinal chemistry and drug design. Metal complexes have shown remarkable clinical results in current cancer therapy. Gold complexes have attained attention due to their high antiproliferative potential. Gold-based drugs are used for the treatment of rheumatoid arthritis. Gold-containing compounds with selective and specific targets are capable to assuage the symptoms of a range of human diseases. Gold (I) species with labile ligands (such as Cl in TEPAuCl) interact with isolated DNA; therefore, this biomolecule has been considered as a target for gold drugs. Gold (I) has a high affinity towards sulfur and selenium. Due to this, gold (I) drugs readily interact with cysteine or selenocysteine residue of the enzyme to form protein-gold(I) thiolate or protein-gold (I) selenolate complexes that lead to inhibition of the enzyme activity. Au(III) compounds due to their square-planner geometriesthe same as found in cisplatin, represent a good source for the development of anti-tumor agents. This article aims to review the most important applications of gold products in the treatment of human colon cancer and to analyze the complex interplay between gold and the human body.
  8. Gokada MR, Pasupuleti VR, Bollikolla HB
    Mini Rev Med Chem, 2021;21(10):1173-1181.
    PMID: 33397236 DOI: 10.2174/1389557521666210104165733
    The novel Coronavirus disease (COVID-19) is an epidemic disease that appeared at the end of the year 2019 with a sudden increase in number and came to be considered as a pandemic disease caused by a viral infection which has threatened most countries for an emergency search for new anti-SARS-COV drugs /vaccines. At present, the number of clinical trials is ongoing worldwide on different drugs i.e. Hydroxychloroquine, Remedisvir, Favipiravir that utilize various mechanisms of action. A few countries are currently processing clinical trials, which may result in a positive outcome. Favipiravir (FPV) represents one of the feasible treatment options for COVID-19, if the result of the trials turns out positive. Favipiravir will be one of the developed possibly authoritative drugs to warrant benefits to mankind with large-scale production to meet the demands of the current pandemic Covid-19 outbreak and future epidemic outbreaks. In this review, the authors tried to explore key molecules, which will be supportive for devising COVID-19 research.
  9. Shirbhate E, Patel P, Patel VK, Veerasamy R, Sharma PC, Sinha BN, et al.
    Mini Rev Med Chem, 2021;21(8):1004-1016.
    PMID: 33280595 DOI: 10.2174/1389557520666201204162103
    The novel coronavirus disease-19 (COVID-19) is a global pandemic that emerged from Wuhan, China, and has spread all around the world, affecting 216 countries or territories with 21,732,472 people infected and 770,866 deaths globally (as per WHO COVID-19 updates of August 18, 2020). Continuous efforts are being made to repurpose the existing drugs and develop vaccines for combating this infection. Despite, to date, no certified antiviral treatment or vaccine exists. Although, few candidates have displayed their efficacy in in vitro studies and are being repurposed for COVID- 19 treatment. This article summarizes synthetic and semi-synthetic compounds displaying potent activity in clinical uses or studies on COVID-19 and also focuses on the mode of action of drugs being repositioned against COVID-19.
  10. Abdullah MA, Mohd Faudzi SM, Nasir NM
    Mini Rev Med Chem, 2021;21(9):1058-1070.
    PMID: 33272171 DOI: 10.2174/1389557520999201203213957
    Medicinal chemists have continuously shown interest in new curcuminoid derivatives, diarylpentadienones, owing to their enhanced stability feature and easy preparation using a one-pot synthesis. Thus far, methods such as Claisen-Schmidt condensation and Julia- Kocienski olefination have been utilised for the synthesis of these compounds. Diarylpentadienones possess a high potential as a chemical source for designing and developing new and effective drugs for the treatment of diseases, including inflammation, cancer, and malaria. In brief, this review article focuses on the broad pharmacological applications and the summary of the structure-activity relationship of molecules, which can be employed to further explore the structure of diarylpentadienone. The current methodological developments towards the synthesis of diarylpentadienones are also discussed.
  11. Faheem, Kumar BK, Sekhar KVGC, Kunjiappan S, Jamalis J, Balaña-Fouce R, et al.
    Mini Rev Med Chem, 2021;21(4):398-425.
    PMID: 33001013 DOI: 10.2174/1389557520666201001130114
    β-Carboline, a naturally occurring indole alkaloid, holds a momentous spot in the field of medicinal chemistry due to its myriad of pharmacological actions like anticancer, antiviral, antibacterial, antifungal, antileishmanial, antimalarial, neuropharmacological, anti-inflammatory and antithrombotic among others. β-Carbolines exhibit their pharmacological activity via diverse mechanisms. This review provides a recent update (2015-2020) on the anti-infective potential of natural and synthetic β-carboline analogs focusing on its antibacterial, antifungal, antiviral, antimalarial, antileishmanial and antitrypanosomal properties. In cases where enough details are available, a note on its mechanism of action is also added.
  12. Sarkar N, Dey YN, Kumar D, Rajagopal M
    Mini Rev Med Chem, 2021;21(19):3037-3051.
    PMID: 34036911 DOI: 10.2174/1389557521666210525120325
    Effective treatment of tuberculosis has been hampered by the emergence of drug-resistant strains of Mycobacterium therapeutic facilities tuberculosis. With the global resurgence of tuberculosis with the development of multidrug-resistant cases, there is a call for the development of new drugs to combat these diseases. Throughout history, natural products have afforded a rich source of compounds that have found many applications in the fields of medicine, pharmacy and biology, and continued to play a significant role in the drug discovery and development process. This review article depicts the various potential plant extracts as well as plant derived phytoconstituents against the H37rv, the most persistent strains of Mycobacterium tuberculosis and its multidrug strains.
  13. Vanessa VV, Mah SH
    Mini Rev Med Chem, 2021;21(17):2507-2529.
    PMID: 33583373 DOI: 10.2174/1389557521666210212152514
    Alzheimer's disease is a neurodegenerative disorder that results in progressive and irreversible central nervous system impairment, which has become one of the severe issues recently. The most successful approach of Alzheimer's treatment is the administration of cholinesterase inhibitors to prevent the hydrolysis of acetylcholine and subsequently improve cholinergic postsynaptic transmission. This review highlights a class of heterocycles, namely xanthone, and its remarkable acetylcholinesterase inhibitory activities. Naturally occurring xanthones, including oxygenated, prenylated, pyrano, and glycosylated xanthones, exhibited promising inhibition effects towards acetylcholinesterase. Interestingly, synthetic xanthone derivatives with complex substituents such as alkyl, pyrrolidine, piperidine, and morpholine have shown greater acetylcholinesterase inhibition activities. The structure-activity relationship of xanthones revealed that the type and position of the substituent(s) attached to the xanthone moiety influenced acetylcholinesterase inhibition activities where hydrophobic moiety will lead to an improved activity by contributing to the π-π interactions, as well as the hydroxy substituent(s) by forming hydrogen-bond interactions. Thus, further studies, including quantitative structure-activity relationship, in vivo and clinical validation studies are crucial for the development of xanthones into novel anti-Alzheimer's disease drugs.
  14. Lew SY, Teoh SL, Lim SH, Lim LW, Wong KH
    Mini Rev Med Chem, 2020;20(15):1518-1531.
    PMID: 32452327 DOI: 10.2174/1389557520666200526125534
    Depression is the most common form of mental illness and the major cause of disability worldwide. Symptoms of depression, including feelings of intense sadness and hopelessness, may occur after a specific event or in response to a gradual decline in health and functional status, often associated with aging. Current therapies for treating these symptoms include antidepressant drugs, counseling and behavioral therapy. However, antidepressant drugs are associated with mild to severe adverse effects, which has prompted the need for better treatment options. Medicinal mushrooms are valuable sources of food and medicine and are increasingly being used as supplements or as alternative medicines in standard healthcare. Numerous studies have provided insights into the neuroprotective effects of medicinal mushrooms, which are attributed to their antioxidant, anti-neuroinflammatory, cholinesterase inhibitory and neuroprotective properties. In this review, we comprehensively examine the role of these medicinal mushrooms in the treatment of depression. However, to apply these natural products in clinical settings, the therapeutic agent needs to be properly evaluated, including the active ingredients, the presence of synergistic effects, efficient extraction methods, and stabilization of the active ingredients for delivery into the body as well as crossing the blood-brain barrier.
  15. Tahlan S, Narasimhan B, Lim SM, Ramasamy K, Mani V, Shah SAA
    Mini Rev Med Chem, 2020;20(15):1559-1571.
    PMID: 30179132 DOI: 10.2174/1389557518666180903151849
    BACKGROUND: Various analogues of benzimidazole are found to be biologically and therapeutically potent against several ailments. Benzimidazole when attached with heterocyclic rings has shown wide range of potential activities. So, from the above provided facts, we altered benzimidazole derivatives so that more potent antagonists could be developed. In the search for a new category of antimicrobial and anticancer agents, novel azomethine of 2-mercaptobenzimidazole derived from 3-(2- (1H-benzo[d]imidazol-2-ylthio)acetamido)benzohydrazide were synthesized.

    RESULTS AND DISCUSSION: The synthesized analogues were characterized by FT-IR, 1H/13C-NMR and MS studies as well C, H, N analysis. All synthesized compounds were evaluated for in vitro antibacterial activity against Gram-positive (B. subtilis), Gram-negative (E. coli, P. aeruginosa, K. pneumoniae and S. typhi) strains and in vitro antifungal activity against C. albicans and A. niger strains by serial dilution method, the minimum inhibitory concentration (MIC) described in μM/ml. The in vitro anticancer activity of synthesized compounds was determined against human colorectal carcinoma cell line (HCT- 116) using 5-fluorouracil as standard drug.

    CONCLUSION: In general, most of the synthesized derivatives exhibited significant antimicrobial and anticancer activities. Compounds 8, 10, 15, 16, 17, 20 and 22 showed significant antimicrobial activity towards tested bacterial and fungal strains and compound 26 exhibited significant anticancer activity.

  16. Abdullahi SA, Unyah NZ, Nordin N, Basir R, Nasir WM, Alapid AA, et al.
    Mini Rev Med Chem, 2020;20(9):739-753.
    PMID: 31660810 DOI: 10.2174/1389557519666191029105736
    Identification of drug target in protozoan T. gondii is an important step in the development of chemotherapeutic agents. Likewise, exploring phytochemical compounds effective against the parasite can lead to the development of new drug agent that can be useful for prophylaxis and treatment of toxoplasmosis. In this review, we searched for the relevant literature on the herbs that were tested against T. gondii either in vitro or in vivo, as well as different phytochemicals and their potential activities on T. gondii. Potential activities of major phytochemicals, such as alkaloid, flavonoid, terpenoids and tannins on various target sites on T. gondii as well as other related parasites was discussed. It is believed that the phytochemicals from natural sources are potential drug candidates for the treatment of toxoplasmosis with little or no toxicity to humans.
  17. AlMatar M, Albarri O, Makky EA, Var I, Köksal F
    Mini Rev Med Chem, 2020;20(18):1908-1916.
    PMID: 32811410 DOI: 10.2174/1389557520666200818211405
    The need for new therapeutics and drug delivery systems has become necessary owing to the public health concern associated with the emergence of multidrug-resistant microorganisms. Among the newly discovered therapeutic agents is cefiderocol, which was discovered by Shionogi Company, Japan as an injectable siderophore cephalosporin. Just like the other β-lactam antibiotics, cefiderocol exhibits antibacterial activity via cell wall synthesis inhibition, especially in Gram negative bacteria (GNB); it binds to the penicillin-binding proteins, but its unique attribute is that it crosses the periplasmic space of bacteria owing to its siderophore-like attribute; it also resists the activity of β-lactamases. Among all the synthesized compounds with the modified C-7 side chain, cefiderocol (3) presented the best and well-balanced activity against multi-drug resistant (MDR) Gram negative bacteria, including those that are resistant to carbapenem. İn this article, an overview of the recent studies on cefiderocol was presented.
  18. Yazit NAA, Juliana N, Das S, Teng NIMF, Fahmy NM, Azmani S, et al.
    Mini Rev Med Chem, 2020;20(17):1781-1790.
    PMID: 32564754 DOI: 10.2174/1389557520666200621182717
    Postoperative Cognitive Dysfunction (POCD) refers to the condition of neurocognitive decline following surgery in a cognitive and sensory manner. There are several risk factors, which may be life-threatening for this condition. Neuropsychological assessment of this condition is very important. In the present review, we discuss the association of apolipoprotein epsilon 4 (APOE ε4) and few miRNAs with POCD, and highlight the clinical importance for prognosis, diagnosis and treatment of POCD. Microarray is a genome analysis that can be used to determine DNA abnormalities. This current technique is rapid, efficient and high-throughout. Microarray techniques are widely used to diagnose diseases, particularly in genetic disorder, chromosomal abnormalities, mutations, infectious diseases and disease-relevant biomarkers. MicroRNAs (miRNAs) are a class of non-coding RNAs that are widely found distributed in eukaryotes. Few miRNAs influence the nervous system development, and nerve damage repair. Microarray approach can be utilized to understand the miRNAs involved and their pathways in POCD development, unleashing their potential to be considered as a diagnostic marker for POCD. This paper summarizes and identifies the studies that use microarray based approaches for POCD analysis. Since the application of microarray in POCD is expanding, there is a need to review the current knowledge of this approach.
  19. Hanim A, Mohamed IN, Mohamed RMP, Das S, Nor NSM, Harun RA, et al.
    Mini Rev Med Chem, 2020;20(17):1696-1708.
    PMID: 32579497 DOI: 10.2174/1389557520666200624122325
    Alcohol use disorder (AUD) is characterized by compulsive binge alcohol intake, leading to various health and social harms. Protein Kinase C epsilon (PKCε), a specific family of PKC isoenzyme, regulates binge alcohol intake, and potentiates alcohol-related cues. Alcohol via upstream kinases like the mammalian target to rapamycin complex 1 (mTORC1) or 2 (mTORC2), may affect the activities of PKCε or vice versa in AUD. mTORC2 phosphorylates PKCε at hydrophobic and turn motif, and was recently reported to be associated with alcohol-seeking behavior, suggesting the potential role of mTORC2-PKCε interactions in the pathophysiology of AUD. mTORC1 regulates translation of synaptic proteins involved in alcohol-induced plasticity. Hence, in this article, we aimed to review the molecular composition of mTORC1 and mTORC2, drugs targeting PKCε, mTORC1, and mTORC2 in AUD, upstream regulation of mTORC1 and mTORC2 in AUD and downstream cellular mechanisms of mTORCs in the pathogenesis of AUD.
  20. Das S, Mohamed IN, Teoh SL, Thevaraj T, Ku Ahmad Nasir KN, Zawawi A, et al.
    Mini Rev Med Chem, 2020;20(7):626-635.
    PMID: 31969099 DOI: 10.2174/1389557520666200122124445
    The incidence of Metabolic Syndrome (MetS) has risen globally. MetS includes a combination of features, i.e. blood glucose impairment, excess abdominal/body fat dyslipidemia and elevated blood pressure. Other than conventional treatment with drugs, the main preventive approaches include lifestyle changes, weight loss, diet control and adequate exercise also proves to be beneficial. MicroRNAs (miRNAs) are small non-coding RNAs that play critical regulatory roles in most biological and pathological processes. In the present review, we discuss various miRNAs which are related to MetS by targeting various organs, including the pancreas, liver, skeletal muscles and adipose tissues. These miRNAs have the effect on insulin production and secretion (miR-9, miR-124a, miR-130a,b, miR152, miR-335, miR-375), insulin resistance (miR-29), adipogenesis (miR-143, miR148a) and lipid metabolism (miR-192). We also discuss the miRNAs as potential biomarkers and future therapeutic targets. This review may be beneficial for molecular biologists and clinicians dealing with MetS.
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