International Journal of Current Research and Review
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IJCRR - Vol 03 Issue 07, July, 2011

Pages: 15-23

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AN INSIGHT INTO METAL BASED ANTI-CANCER DRUGS

Author: Raj Kaushal, Nitesh Kumar, Rajeev Kaushal, Pamita Awasthi

Category: Healthcare

Abstract:Metal complexes play critical role in the treatment of cancer. Cis-platin which is model anticancer drug has been used in the treatment of various types of cancer. But due to its side effects and resistance phenomenon efforts have been made to explore the possibility of synthesizing novel non-platinum based anti-cancer drugs. In addition to platinum based drugs, complexes of other transition metals like titanium, ruthenium, palladium and gold etc. also show pronounced anti-cancer activity. The Complexes with titanium and ruthenium have already been evaluated in phase I and phase II clinical trials. Some transition metal complexes show good anticancer activity against cis-platin resistant cell lines. This review will provide an insight into various platinum as well as non-platinum based anti-cancer drugs.

Keywords: Transition metal, cis-platin, Nucleic acid, protein, platinum, titanium, ruthenium, palladium, gold, anti-cancer, drug, amines, biological activity.

Full Text:

INTRODUCTION

Metals play an important role in our daily life due to their incorporation in our diet in varying quantities1,2. Due to potential pharmacological applications of transition metal based complexes such as antidiabetic, anti-neurological, anti-bacterial, anti-fungal, anti-cancer agents, metal complexes have been used in medicinal chemistry since sixteenth century. Transition metals have tendency to form variety of complexes due to the presence of vacant d-orbitals in their valence shell. They can take part in various biological processes which show their interaction with electron rich biological components like proteins and nucleic acid because metal centers are positively charged and favored to attack on negatively charged biomolecules3-6 . Various transition metals such as platinum(Pt), titanium(Ti), ruthenium(Ru), rhodium(Rh), iridium(Ir), molybdenum(Mo), copper(Cu) and gold(Au) in their complex form are effective against solid tumors in animals and human beings. The first metal complex discovered to exhibit anti-cancer activity was cis-platin (cisdiaminedichloroplatinum(II)). This drug is considered best for treatment of certain types of cancers but due to its toxicity, its utilization has been limited at broad range7- 9 . In coming era, interest has been growing in developing non-platinum based anticancer drugs due to their less toxicity.

Also, non-platinum compounds may provide different oxidation states, coordination geometries, and affinities for certain types of biological ligands10 . It has been established that ligands having O, N, S in their stem showed increased biological activity due to increase in coordination capacity11,12. It has been reported in literature that due to the symmetry of ligand(s) uptake of drug by cancerous cells has been increased13. The necessary conditions for a complex to have anti cancer activities are as i) Complex should be neutral so that it can diffuse through the hydrophobic cell membrane. ii) Complex should have square planer structure i.e. leaving group should be at cis-position. iii) Leaving groups should be labile, so that they can be easily substituted. iv) Groups which are not substituted should have low trans effect like NH3 , heterocyclic amines or diamines14. Amine ligands influence the anti-cancer property, because non leaving amine ligands are the reason for anti-cancer property15. Recently, some non metallocene titanium complexes having oxygen based ligands have been synthesized and it has been established that ligand lability is not essential to show anti-tumor activity16 .

Platinum Complexes as anti cancer agents:

The first metal based anticancer drug discovered was Cisdiaminedichloroplatinum(II) (cis-platin) by Rosenberg et al8,9.Cis-platin acts by interacting with DNA (Deoxy ribo nucleic acid) via cross linking with two adjacent guanine molecules, followed by the replacement of two chloride groups by water molecules and form aquated cisplatin which stops the replication of DNA and obstruct the cell growth which is the ultimate aim of anti- cancer drugs14. Cisplatin has been used in the treatment of various types of cancers such as testicular, ovarian, lung, neck, and head cancers. This metal complex used in the treatment of various cancerous malignancies and is one of the best-selling anti-cancer drug all over the world. Cis-platin has several disadvantages some of which may include that by treating the cells with cis-platin, necrotic and apoptic cell death occur simultanesly. Also, it has limited solubility in water hence it is given intravenously to reduce the harm to the kidney. Other side effects of using cis-platin are emesis, nausea, vomiting, nephrotoxicity, neurotoxicity, myelosuppression, ototoxicity14 . Also only a limited number of tumors can be treated with platinum based drugs. In addition to cis-platin many other platinum based drugs (Carboplatin, Oxaliplatin, nedaplatin and lobaplatin) passed for current tumor therapy1 . The new platinum complexes of the formula [Pt(2,2'- bipyridine)amino acid] n+ where n =1-2 and amino acid is an anion of L-histidine, LLysine, L-asparagine, L-tryptophan, or Ltyrosine, had been prepared by interaction of [Pt(2,2'-bipyridine)Cl2] and an appropriate amino acid (sodium salt) in water or water-methanol mixture which are highly negatively charged molecules. In case of Histidine the Platinum atom binds with –NH2 group of Histidine and in case of other amino acids Platinum binds by NH2 and COOgroups and these complexes were used against P-388 Lymphocytic leukemic cells18. An octahedral complex of Platinum(IV) with adamantylamine of composition bis(acetato)(1- adamantylamine)amminedichloro platinum(IV) had been prepared and showed resistance factor 2.84 fold lower than cis-platin because adamantylamine is a bulky hydrophobic ligand and the use increase the uptake of compound by the cancerous cells and able to overcome the acquired cis-platin resistance13. Pt(IV) complex with adamantylamine penetrate as a whole complex inside the cell membrane. It may be due to hydrophobicity of ligand. The symmetry of hydrophobic adamntylamine ligand lightens the penetration of whole complex inside the cell membrane. The penetration of Pt(IV) complex with adamantylamine had been improved and facilitates transport across cell membrane. This hydrophobic ligand enhances accumulation inside cancer cell and trigger rapid cell death in both cisplatin sensitive and cis-platin resistant cell lines15 . The Pt(II) Complexes bearing pyridine carboxyldimines containing bulky aromatic groups examined for their potential cytotoxicites against human ovarian carcinoma and cis-platin resistant cell line19. A series of trans-platinum(IV) complexes with functionalized aromatic carboxylate ligands cis, cis, transPt(NH3 ) 2Cl2 (CO2C6H4R)2 where R may be H, p-vinyl, p-methoxy, p-iodo, p-cyano, pcarboxyl had been synthesized and due to presence of aryl groups uptake of drugs had been improved and facilitate transport across cell membrane. These complexes were evaluated for cellular uptake and inhibition of cell proliferation against a panel of lung, colon and breast carcinoma cell lines20 .

Gold Compounds having anti-cancer activities:

The interaction of cytotoxic gold(III) compounds with DNA is weak than that of platinum analogues but gold(III) complexes have good interaction with model proteins and target proteins. The mode of action of gold(III) compounds is significantly different than that of cis-platin. Some compounds like [Au(en2)]Cl3 (en=ethylene diamine), [Au(dien)Cl]Cl2 (dien=diethylene diamine), [Au(cyclam)](ClO4) 2Cl, [Au(terpy)Cl]Cl2 (terpy=terpyridine), and [Au(phen)Cl2]Cl (phen=phenanthroline) were characterized in solid state and in solution. These compounds of gold were tested on human ovarian cell line A2780,which were either sensitive or resistance to cis-platin21. A new compound Chloro-glycylhistidinate gold(III) (GHAu) had good biological property and tested for cytotoxic properties in vitro against MOLT-4 (human leukemia) and C2C12 (mouse tumor) cell lines22,23 . Nowadays, gold(III) compounds are good cytotoxic agents. Plenty of gold(III) compounds were characterized and synthesized in the last fifteen years24. Gold complexes containing bipyridine ligands of general formula [Au(NΛN)Cl2]PF6 where (NΛN) = 2,2'-bipyridine, 4,4'-dimethyl bipyridine, 4,4'-dimethoxy-2,2'-bipyridine, 4,4'-diamino-2,2'-bipyridine showed moderate to good cytotoxicity in vitro towards human ovarian carcinoma cell line and cis-platin resistance variant25 .

RUTHENIUM COMPLEXES:

Ruthenium complexes have attracted much attention as building blocks for new transition metal based anti-tumor agents. Ruthenium compounds offer the potential over anti-tumor platinum(II) complexes currently used in the clinic because of reduced toxicity, a novel mechanism of action and the prospect of non cross resistance26-29. Organo ruthenium complexes due to presence of lipophilic arene can interact better than that of cisplatin inside the cell, by causing chlorine dissociation which is an important factor for cell death. Ruthenium(III) complexes of general formula [Ru(η 6 - arene)Cl2(NC5H4OOC-C5H4 FeC5H5)] where arene may be C6H6, C6H5Me, pPrC6H4Me, and C6Me6 and of formula [Ru(η 6 -arene)Cl2]2 (NC5H4OOC- RUTHENIUM COMPLEXES: Ruthenium complexes have attracted much attention as building blocks for new transition metal based anti-tumor agents. Ruthenium compounds offer the potential over anti-tumor platinum(II) complexes currently used in the clinic because of reduced toxicity, a novel mechanism of action and the prospect of non cross resistance26-29. Organo ruthenium complexes due to presence of lipophilic arene can interact better than that of cisplatin inside the cell, by causing chlorine dissociation which is an important factor for cell death. Ruthenium(III) complexes of general formula [Ru(η 6 - arene)Cl2(NC5H4OOC-C5H4 FeC5H5)] where arene may be C6H6, C6H5Me, pPrC6H4Me, and C6Me6 and of formula [Ru(η 6 -arene)Cl2]2 (NC5H4OOC-

Palladium Complexes:

The marginal anti-tumor activities of the palladium complexes were explained on the basis of fast reactivities of leaving groups as the reactivity of palladium(II) complexes is much higher as compared to platinum(II) complexes e.g. the reactivity of palladium(II) complexes having 1,2- Diaminocyclohexne and dicarboxylate ligands was 105 times more than that of platinum(II) complexes having similar ligands34 . The Pd(II) complexes of the form trans-PdCl2L2(where L=3- hydroxypyridine, 2-hydroxypyridine, 4- hydroxypyridine) had been synthesized and it had been found that the Solubility, reactivity, electronic and steric properties can be modified by varying the geometry and ligands around the metal center. Out of these the compound of 2-Hydroxy pyridine was found to be most active against A2780, A2780cisR and A2780ZD0473R ovarian cancer cell lines. It had been found that both metal and ligand take part in biological activity of the complex but due to the rapid hydrolysis of palladium complexes (105 faster that Platinum analogues), they dissociate easily before reaching their pharmacological target35 . The platinum(II) and palladium(II) complexes of 2,2'-bipyridine (bipy) with ethyl dithio carbamate (Et-dtc) in which the di thio carbamate ligand coordinate with pt(II) or pd(II) center as bidentate with two sulphur atoms were water soluble and were tested for their in vitro antitumor activity against chronic myllogenous leukemia cell line K562. But these complexes show cytotoxic concentration (Cc50) values lower than that of cis-platin. The mode of interaction of these complexes were investigated by circular-dichromism, ultraviolet difference and flouroscence spectroscopy. The interaction of Pd(II) complex with DNA and its anti- tumor activity against K562 is more than that of its Pt(II) analog36 . The series of palladium complexes with Salicyldamine thio semicarbazone having formula [pd(salt scR)PPh3], {H2Salt scR = Salicyldehyde thio semicarbazone R=H, 3-tert butyl, 3- methoxy, 5-chloro} were prepared by reaction of appropriate salicyldamine thiosemicarbazone with Pd(PPh3)2 in which thiosemicarbazone coordinate to the palladium in a tridentate manner that is through phenolic oxygen, imine nitrogen and thionate sulphur forming five or six membered chelate rings with in the structure and the fourth coordination site is occupied by PPh3. The biological activity of thiosemicarbazone ligand and palladium complexes were investigated towards WHC01 oesophageal cancer cell line and against two strains of malarial parasite plasmodium Falciparum W2 (Chloroquinone resistant)37 . Another palladium(II) compound with 5-methyl uracil of the general formula PdL2Cl2 where L= 5-methyl uracil was prepared by Anshu Srivastava et. al. and it had been found that this light brown compound was hygroscopic and had thermal stability up to 260?C with anti-tumor activity38 .

Titanium based anti-cancer drugs:

In the last few years there has been growing interest in developing nonplatinum based anti-cancer agents due to their pronounced biological activity39-51 . After the discovery of cis-platin, the first non-platinum anti-cancer drugs were budotitane and titanocene dichloride which are titanium based anti cancer drugs. Since titanium is second most abundant transition metal and ninth of all the elements on earth and pure titanium and titanium alloy are widely used for orthopedic and dental implants. Titanium is present in many biomaterials such as food in the form of whitening pigment. So it may incorporated in drugs and in to living systems with low toxicity10. Also Ti(IV) is an oxophillic metal and form strong bond with acidic DNA as well as other biological molecules. Titanium as a metal posseses a wide spectrum of anti-tumor properties. Titanium based compounds i.e. bis (β- diketonato)titanium(IV) [Budotitane] and titanocene derivatives offer an alterative for cancer chemotherapy. The anti-tumor activity of budotitane was reported in 1982.This was first non-platinum complex tested in clinical trials and used against ascites and solid tumor. This drug had maximum tolerable dose of 230 mg on two week schedule with side effects of cardiac arrhythmia. It had been reported that doses higher than maximum tolerable result in liver and kidney toxicity52 . Erich Dubler had synthesized and crystallized di-chloro derivatives of budotitane and found that anti-tumor activity appear due to unsubstituted phenyl rings, if phenyl rings get replaced by methyl groups, activity totally disappears53. The first metallocene i.e. titanocene dichloride show anti-tumor activity against colon, lung and breast cancer although the mechanism of cytotoxicity is not clear yet. This complex also exhibits antiproliferative activity against solid ascite tumor. Titanocene dichloride show anti-tumor activity against doxorubicin and cis-platin resistant ovarian carcinoma cells and also less toxic effect than cis-platin. The advantage of this complex is that no evidence of nephrotoxicity or myolotoxicity had been reported. It has been found in literature that studies on chemistry of titanium as anti tumor agent are more limited52. Titanocene dichloride are proved to be superior compounds of its derivatives since in addition to anti-tumor properties titanocene dichloride exhibits anti-viral54, antiarithmetic, and anti-inflammatory activities55. This compound exhibits higher toxicity than cis-platin, doxorubicin, mitoxantrone and vinblastine in human renal cell carcinoma. The other halides or pseudohalides of Cp2TiX2 (where X=F, Br, I, NCS, N3) were tested for ehrlich ascite tumor in mice and show anti proliferative activity similar to Cp2TiCl2. Budotitane and titanocene dichloride possess same limitation that they have low hydrolytic stability at physiological pH52 . In this respect titanium(IV) complexes offer a new outlook for chemotherapy. The novel titanocene compounds are better than cis-platin for apoptic effect in vitro and they can induce more apoptosis than cisplatin. TitanoceneY (bis-[(pmethoxybenzyl) cyclopentadienyl titanium dichloride) had better effect in prostate, pancreas, breast and ovarian cell lines and in uterine and renal cancer cells56 . Michael shavit et al studied Ti(IV) complexes of oxygen-based ligands. They had prepared the homoleptic complex of hydroxyamino 1,3,5 triazine ligands. These triazine ligands possess mild reactivity despite having no labile groups. This complex was effective against colon and ovarian cancer cells16 . Since titanocene dichloride is active against colorectal, lung and breast carcinomas, new derivatives may have antitumor activity profile. These complexes have advantage that they do not show common side effects such as emesis, alopecia, or bone marrow impairment52 . These features make titanium compounds interesting for combined therapy and further study16 . The novel achiral titanocene (Titanocene C and Titanocene Y) anti-cancer drug are almost ten times less toxic than cis-platin. The antiproliferative activity of titanocene Y had been studied in 36 human tumor cell lines and in explanted human tumors and albumin was the carrier protein to take titanocene at the target place inside the cell. Prostate, cervix and renal cell cancer were prime target of these titanocene57 . Titanocene dichloride react with trimethyl tin fluoride giving a new class of cytotoxic active substance in which Ti-F bond is 75 Kcal/mol more stable than Ti-Cl bond and due to fluorides ions product were not cytotoxic at concentration below 10-3M. But the drawback of this complex was that they show instability in water solution58 . Also titanocenyl amide complex having triflouromethoxy group on para position show more cytotoxicity than titanocene dichloride due to –OCF3 group on Para position and more stability in aqueous solution. Different compounds were synthesized by replacing –OCF3 by another groups and these were found active against breast cancer cell line MCF-7 59 . In addition to these, titanium alkoxide complex show toxicity in breast, colon and pancreatic cancer cell lines but molecular mechanism yet to be elucidated60 .

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A Study by Humaira Tahir et al. entitled "Comparison of First Analgesic Demand after Major Surgeries of Obstetrics and Gynecology between Pre-Emptive Versus Intra-Operative Groups by Using Intravenous Paracetamol: A Cross-Sectional Study" is awarded Best Article for Vol 14 issue 14
A Study by Monica K. entitled "Risk Predictors for Lymphoma Development in Sjogren Syndrome - A Systematic Review" is awarded Best Article for Vol 14 issue 13
A Study by Mokhtar M Sh et al. entitled "Prevalence of Hospital Mortality of Critically Ill Elderly Patients" is awarded Best Article for Vol 14 issue 12
A Study by Vidya S. Bhat et al. entitled "Effect of an Indigenous Cleanser on the Microbial Biofilm on Acrylic Denture Base - A Pilot Study" is awarded Best Article for Vol 14 issue 11
A Study by Pandya S. et al. entitled "Acute and 28-Day Repeated Dose Subacute Toxicological Evaluation of Coroprotect Tablet in Rodents" is awarded Best Article for Vol 14 issue 10
A Study by Muhammad Zaki et al. entitled "Effect of Hemoglobin Level on the Severity of Acute Bronchiolitis in Children: A Case-Control Study" is awarded Best Article for Vol 14 issue 09
A Study by Vinita S & Ayushi S entitled "Role of Colour Doppler and Transvaginal Sonography for diagnosis of endometrial pathology in women presenting with Abnormal Uterine Bleeding" is awarded Best Article for Vol 14 issue 08
A Study by Prabhu A et al. entitled "Awareness of Common Eye Conditions among the ASHA (Accredited Social Health Activist) Workers in the Rural Communities of Udupi District- A Pilot Study" is awarded Best Article for Vol 14 issue 07
A Study by Divya MP et al. entitled "Non-Echoplanar Diffusion-Weighted Imaging and 3D Fiesta Magnetic Resonance Imaging Sequences with High Resolution Computed Tomography Temporal Bone in Assessment and Predicting the Outcome of Chronic Suppurative Otitis Media with Cholesteatoma" is awarded Best Article for Vol 14 issue 06
A Study by Zahoor Illahi Soomro et al. entitled "Functional Outcomes of Fracture Distal Radius after Fixation with Two Different Plates: A Retrospective Comparative Study" is awarded Best Article for Vol 14 issue 05
A Study by Ajai KG & Athira KN entitled "Patients’ Gratification Towards Service Delivery Among Government Hospitals with Particular Orientation Towards Primary Health Centres" is awarded Best Article for Vol 14 issue 04
A Study by Mbungu Mulaila AP et al. entitled "Ovarian Pregnancy in Kindu City, D.R. Congo - A Case Report" is awarded Best Article for Vol 14 issue 03
A Study by Maryam MJ et al. entitled "Evaluation Serum Chemerin and Visfatin Levels with Rheumatoid Arthritis: Possible Diagnostic Biomarkers" is awarded Best Article for Vol 14 issue 02
A Study by Shanthan KR et al. entitled "Comparison of Ultrasound Guided Versus Nerve Stimulator Guided Technique of Supraclavicular Brachial Plexus Block in Patients Undergoing Upper Limb Surgeries" is awarded Best Article for Vol 14 issue 01
A Study by Amol Sanap et al. entitled "The Outcome of Coxofemoral Bypass Using Cemented Bipolar Hemiarthroplasty in the Treatment of Unstable Intertrochanteric Fracture of Femur in a Rural Setup" is awarded Best Article Award of Vol 13 issue 24
A Study by Manoj KP et al. entitled "A Randomized Comparative Clinical Trial to Know the Efficacy of Ultrasound-Guided Transversus Abdominis Plane Block Against Multimodal Analgesia for Postoperative Analgesia Following Caesarean Section" is awarded Best Article Award of Vol 13 issue 23
A Study by Karimova II et al. entitled "Changes in the Activity of Intestinal Carbohydrases in Alloxan-Induced Diabetic Rats and Their Correction with Prenalon" is awarded Best Article of Vol 13 issue 22
A Study by Ashish B Roge et al. entitled "Development, Validation of RP-HPLC Method and GC MS Analysis of Desloratadine HCL and It’s Degradation Products" is awarded Best Article of Vol 13 issue 21
A Study by Isha Gaurav et al. entitled "Association of ABO Blood Group with Oral Cancer and Precancer – A Case-control Study" is awarded Best Article for Vol 13 issue 20
A Study by Amr Y. Zakaria et al. entitled "Single Nucleotide Polymorphisms of ATP-Binding Cassette Gene(ABCC3 rs4793665) affect High Dose Methotrexate-Induced Nephrotoxicity in Children with Osteosarcoma" is awarded Best Article for Vol 13 issue 19
A Study by Kholis Ernawati et al. entitled "The Utilization of Mobile-Based Information Technology in the Management of Dengue Fever in the Community Year 2019-2020: Systematic Review" is awarded Best Article for Vol 13 issue 18
A Study by Bhat Asifa et al. entitled "Efficacy of Modified Carbapenem Inactivation Method for Carbapenemase Detection and Comparative Evaluation with Polymerase Chain Reaction for the Identification of Carbapenemase Producing Klebsiella pneumonia Isolates" is awarded Best Article for Vol 13 issue 17
A Study by Gupta R. et al. entitled "A Clinical Study of Paediatric Tracheostomy: Our Experience in a Tertiary Care Hospital in North India" is awarded Best Article for Vol 13 issue 16
A Study by Chandran Anand et al. entitled "A Prospective Study on Assessment of Quality of Life of Patients Receiving Sorafenib for Hepatocellular Carcinoma" is awarded Best article for Vol 13 issue 15
A Study by Rosa PS et al. entitled "Emotional State Due to the Covid – 19 Pandemic in People Residing in a Vulnerable Area in North Lima" is awarded Best Article for Vol 13 issue 14
A Study by Suvarna Sunder J et al. entitled "Endodontic Revascularization of Necrotic Permanent Anterior Tooth with Platelet Rich Fibrin, Platelet Rich Plasma, and Blood Clot - A Comparative Study" is awarded Best Article for Vol 13 issue 13
A Study by Mona Isam Eldin Osman et al. entitled "Psychological Impact and Risk Factors of Sexual Abuse on Sudanese Children in Khartoum State" is awarded Best Article for Vol 13 issue 12
A Study by Khaw Ming Sheng & Sathiapriya Ramiah entitled "Web Based Suicide Prevention Application for Patients Suffering from Depression" is awarded Best Article for Vol 13 issue 11
A Study by Purushottam S. G. et al. entitled "Development of Fenofibrate Solid Dispersions for the Plausible Aqueous Solubility Augmentation of this BCS Class-II Drug" is awarded Best article for Vol 13 issue 10
A Study by Kumar S. et al. entitled "A Study on Clinical Spectrum, Laboratory Profile, Complications and Outcome of Pediatric Scrub Typhus Patients Admitted to an Intensive Care Unit from a Tertiary Care Hospital from Eastern India" is awarded Best Article for Vol 13 issue 09
A Study by Mardhiah Kamaruddin et al. entitled "The Pattern of Creatinine Clearance in Gestational and Chronic Hypertension Women from the Third Trimester to 12 Weeks Postpartum" is awarded Best Article for Vol 13 issue 08
A Study by Sarmila G. B. et al. entitled "Study to Compare the Efficacy of Orally Administered Melatonin and Clonidine for Attenuation of Hemodynamic Response During Laryngoscopy and Endotracheal Intubation in Gastrointestinal Surgeries" is awarded Best Article for Vol 13 issue 07
A Study by M. Muthu Uma Maheswari et al. entitled "A Study on C-reactive Protein and Liver Function Tests in Laboratory RT-PCR Positive Covid-19 Patients in a Tertiary Care Centre – A Retrospective Study" is awarded Best Article of Vol 13 issue 06 Special issue Modern approaches for diagnosis of COVID-19 and current status of awareness
A Study by Gainneos PD et al. entitled "A Comparative Evaluation of the Levels of Salivary IgA in HIV Affected Children and the Children of the General Population within the Age Group of 9 – 12 Years – A Cross-Sectional Study" is awarded Best Article of Vol 13 issue 05 Special issue on Recent Advances in Dentistry for better Oral Health
A Study by Alkhansa Mahmoud et al. entitled "mRNA Expression of Somatostatin Receptors (1-5) in MCF7 and MDA-MB231 Breast Cancer Cells" is awarded Best Article of Vol 13 issue 06
A Study by Chen YY and Ghazali SRB entitled "Lifetime Trauma, posttraumatic stress disorder Symptoms and Early Adolescence Risk Factors for Poor Physical Health Outcome Among Malaysian Adolescents" is awarded Best Article of Vol 13 issue 04 Special issue on Current Updates in Plant Biology to Medicine to Healthcare Awareness in Malaysia
A Study by Kumari PM et al. entitled "Study to Evaluate the Adverse Drug Reactions in a Tertiary Care Teaching Hospital in Tamilnadu - A Cross-Sectional Study" is awarded Best Article for Vol 13 issue 05
A Study by Anu et al. entitled "Effectiveness of Cytological Scoring Systems for Evaluation of Breast Lesion Cytology with its Histopathological Correlation" is awarded Best Article of Vol 13 issue 04
A Study by Sharipov R. Kh. et al. entitled "Interaction of Correction of Lipid Peroxidation Disorders with Oxibral" is awarded Best Article of Vol 13 issue 03
A Study by Tarek Elwakil et al. entitled "Led Light Photobiomodulation Effect on Wound Healing Combined with Phenytoin in Mice Model" is awarded Best Article of Vol 13 issue 02
A Study by Mohita Ray et al. entitled "Accuracy of Intra-Operative Frozen Section Consultation of Gastrointestinal Biopsy Samples in Correlation with the Final Histopathological Diagnosis" is awarded Best Article for Vol 13 issue 01
A Study by Badritdinova MN et al. entitled "Peculiarities of a Pain in Patients with Ischemic Heart Disease in the Presence of Individual Combines of the Metabolic Syndrome" is awarded Best Article for Vol 12 issue 24
A Study by Sindhu Priya E S et al. entitled "Neuroprotective activity of Pyrazolone Derivatives Against Paraquat-induced Oxidative Stress and Locomotor Impairment in Drosophila melanogaster" is awarded Best Article for Vol 12 issue 23
A Study by Habiba Suhail et al. entitled "Effect of Majoon Murmakki in Dysmenorrhoea (Usre Tams): A Standard Controlled Clinical Study" is awarded Best Article for Vol 12 issue 22
A Study by Ghaffar UB et al. entitled "Correlation between Height and Foot Length in Saudi Population in Majmaah, Saudi Arabia" is awarded Best Article for Vol 12 issue 21
A Study by Siti Sarah Binti Maidin entitled "Sleep Well: Mobile Application to Address Sleeping Problems" is awarded Best Article for Vol 12 issue 20
A Study by Avijit Singh"Comparison of Post Operative Clinical Outcomes Between “Made in India” TTK Chitra Mechanical Heart Valve Versus St Jude Mechanical Heart Valve in Valve Replacement Surgery" is awarded Best Article for Vol 12 issue 19
A Study by Sonali Banerjee and Mary Mathews N. entitled "Exploring Quality of Life and Perceived Experiences Among Couples Undergoing Fertility Treatment in Western India: A Mixed Methodology" is awarded Best Article for Vol 12 issue 18
A Study by Jabbar Desai et al. entitled "Prevalence of Obstructive Airway Disease in Patients with Ischemic Heart Disease and Hypertension" is awarded Best Article for Vol 12 issue 17
A Study by Juna Byun et al. entitled "Study on Difference in Coronavirus-19 Related Anxiety between Face-to-face and Non-face-to-face Classes among University Students in South Korea" is awarded Best Article for Vol 12 issue 16
A Study by Sudha Ramachandra & Vinay Chavan entitled "Enhanced-Hybrid-Age Layered Population Structure (E-Hybrid-ALPS): A Genetic Algorithm with Adaptive Crossover for Molecular Docking Studies of Drug Discovery Process" is awarded Best article for Vol 12 issue 15
A Study by Varsha M. Shindhe et al. entitled "A Study on Effect of Smokeless Tobacco on Pulmonary Function Tests in Class IV Workers of USM-KLE (Universiti Sains Malaysia-Karnataka Lingayat Education Society) International Medical Programme, Belagavi" is awarded Best article of Vol 12 issue 14, July 2020
A study by Amruta Choudhary et al. entitled "Family Planning Knowledge, Attitude and Practice Among Women of Reproductive Age from Rural Area of Central India" is awarded Best Article for special issue "Modern Therapeutics Applications"
A study by Raunak Das entitled "Study of Cardiovascular Dysfunctions in Interstitial Lung Diseas epatients by Correlating the Levels of Serum NT PRO BNP and Microalbuminuria (Biomarkers of Cardiovascular Dysfunction) with Echocardiographic, Bronchoscopic and HighResolution Computed Tomography Findings of These ILD Patients" is awarded Best Article of Vol 12 issue 13 
A Study by Kannamani Ramasamy et al. entitled "COVID-19 Situation at Chennai City – Forecasting for the Better Pandemic Management" is awarded best article for  Vol 12 issue 12
A Study by Muhammet Lutfi SELCUK and Fatma entitled "Distinction of Gray and White Matter for Some Histological Staining Methods in New Zealand Rabbit's Brain" is awarded best article for  Vol 12 issue 11
A Study by Anamul Haq et al. entitled "Etiology of Abnormal Uterine Bleeding in Adolescents – Emphasis Upon Polycystic Ovarian Syndrome" is awarded best article for  Vol 12 issue 10
A Study by entitled "Estimation of Reference Interval of Serum Progesterone During Three Trimesters of Normal Pregnancy in a Tertiary Care Hospital of Kolkata" is awarded best article for  Vol 12 issue 09
A Study by Ilona Gracie De Souza & Pavan Kumar G. entitled "Effect of Releasing Myofascial Chain in Patients with Patellofemoral Pain Syndrome - A Randomized Clinical Trial" is awarded best article for  Vol 12 issue 08
A Study by Virendra Atam et. al. entitled "Clinical Profile and Short - Term Mortality Predictors in Acute Stroke with Emphasis on Stress Hyperglycemia and THRIVE Score : An Observational Study" is awarded best article for  Vol 12 issue 07
A Study by K. Krupashree et. al. entitled "Protective Effects of Picrorhizakurroa Against Fumonisin B1 Induced Hepatotoxicity in Mice" is awarded best article for issue Vol 10 issue 20
A study by Mithun K.P. et al "Larvicidal Activity of Crude Solanum Nigrum Leaf and Berries Extract Against Dengue Vector-Aedesaegypti" is awarded Best Article for Vol 10 issue 14 of IJCRR
A study by Asha Menon "Women in Child Care and Early Education: Truly Nontraditional Work" is awarded Best Article for Vol 10 issue 13
A study by Deep J. M. "Prevalence of Molar-Incisor Hypomineralization in 7-13 Years Old Children of Biratnagar, Nepal: A Cross Sectional Study" is awarded Best Article for Vol 10 issue 11 of IJCRR
A review by Chitra et al to analyse relation between Obesity and Type 2 diabetes is awarded 'Best Article' for Vol 10 issue 10 by IJCRR. 
A study by Karanpreet et al "Pregnancy Induced Hypertension: A Study on Its Multisystem Involvement" is given Best Paper Award for Vol 10 issue 09

List of Awardees

A Study by Ese Anibor et al. "Evaluation of Temporomandibular Joint Disorders Among Delta State University Students in Abraka, Nigeria" from Vol 13 issue 16 received Emerging Researcher Award


A Study by Alkhansa Mahmoud et al. entitled "mRNA Expression of Somatostatin Receptors (1-5) in MCF7 and MDA-MB231 Breast Cancer Cells" from Vol 13 issue 06 received Emerging Researcher Award


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International Journal of Current Research and Review (IJCRR) provides platform for researchers to publish and discuss their original research and review work. IJCRR can not be held responsible for views, opinions and written statements of researchers published in this journal

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