View PDF Version
Total Page：16
File Type：pdf, Size：1020Kb
RSC Advances View Article Online REVIEW View Journal | View Issue Two decades of antifilarial drug discovery: a review a b a Cite this: RSC Adv.,2017,7,20628 Jaiprakash N. Sangshetti, * Devanand B. Shinde, Abhishek Kulkarni and Rohidas Arotec Filariasis is one of the oldest, most debilitating, disabling, and disfiguring neglected tropical diseases with various clinical manifestations and a low rate of mortality, but has a high morbidity rate, which results in social stigma. According to the WHO estimation, about 120 million people from 81 countries are Received 14th February 2017 infected at present and an estimated 1.34 billion people live in areas endemic to filariasis and are at risk Accepted 31st March 2017 of infection. In this review, we focus on Lymphatic Filariasis (LF) and provide brief insights on some other DOI: 10.1039/c7ra01857f filarial conditions. Current drug treatments have beneficial effects in the elimination of only the larval rsc.li/rsc-advances stage of the worms. Very few drugs are available for treatment of filariasis but their repetitive use may aY. B. Chavan College of Pharmacy, Dr. Raq Zakaria Campus, Rauza Baugh, cDepartment of Molecular Genetics, School of Dentistry, Seoul National University, Aurangabad-(MS), India. E-mail: jnsangshetti@rediffmail.com Seoul, Republic of Korea Creative Commons Attribution 3.0 Unported Licence. bShivaji University, Kolhapur (MS), India Dr Jaiprakash N. Sangshetti Dr Devanand B. Shinde is pres- graduated from Y.B. Chavan ently working as a vice chan- College of Pharmacy, Aur- cellor of Shivaji University, angabad (MS), INDIA in 1999. Kolhapur (MS) India. He is He has completed M. Pharmacy NAMASTE Visiting Scholar to This article is licensed under a from Prin. K. M. Kundnani University of Oxford, 2017. College of Pharmacy, Mumbai. Previously he was working as He obtained his PhD degree a Professor of Pharmaceutical from Dr Babasaheb Ambedkar Chemistry, Department of Open Access Article. Published on 11 April 2017. Downloaded 9/29/2021 12:30:02 AM. Marathwada University, Aur- Chemical Technology, Dr Baba- angabad under the supervision saheb Amberdkar Marathwada of Dr Devanand B. Shinde in University Aurangabad, India. 2009. Since 2010 he is working He has more than 27 years of as Associate Professor at Y.B. Chavan College of Pharmacy, Aur- research experience in synthetic organic chemistry, Medicinal angabad (MS), INDIA. He has Three Patents to his credit and has Chemistry particularly in synthesis of molecules having biological published more than 125 research papers in International Jour- and commercial importance. He obtained his PhD degree from Dr nals. He has authored Two Books one on Pharmaceutical Valida- Babasaheb Ambedkar Marathwada University Aurangabad in tion and other on Quality by design. He is a Recipient of Young 1991. He has ve Patents (03 granted and 02 published) to his Scientist Award from Department of Science and Technology credit and has published more than 250 research papers in INDIA. He has received research grant from different funding International Journals. He has authored Four Books. He is agencies like DST, UGC and AICTE. His major area of research a Recipient of UGC-BSR-One time Grant under FRP Scheme. He includes design and synthesis of bioactive molecules, development has received research grant from different funding agencies like & validation of analytical methods for drugs & pharmaceutical DST, UGC, ICMR, CSIR and AICTE. He has guided 20 students for dosage forms. He is currently working on the different targets in PhD and 03 students are currently working for PhD. He is an antibacterial drug discovery. elected fellow of the Maharashtra Academy of Sciences. He has received CSIR award for Short lm on Need of New Drugs for Tuberculosis in 2014. He has Developed process for small scale manufacturing of 30 (Fine Chemicals) and industrial process for 11 API for Pharmaceutical Industry. He is currently working on the different targets in antileishmanial, antibacterial, anticancer drug discovery. 20628 | RSC Adv.,2017,7,20628–20666 This journal is © The Royal Society of Chemistry 2017 View Article Online Review RSC Advances give rise to drug resistance. They are also found to be fairly ineffective towards eliminating adult worms. Moreover, no effective vaccine is available for treatment of filariasis. Because of these limitations, development of new antifilarials has been of utmost importance, a fact which encourages researchers to discover new drugs having antifilarial activity. Herein we extensively review developments in the field of antifilarials including the types of filariasis, their historical perspectives, eradication programs, different classes of drug (i.e. synthetic as well as natural), explored product-derived different targets, patents and clinical trials. Introduction or genitals, causing signicant pain, loss of productivity and social isolation.5,6 “Overcoming neglected tropical diseases (NTDs) make sense Filariasis exhibits various clinical manifestations depending both for economies and for development. The prospects for on various factors such as vector, host immune response, – success have never been so strong. Millions of people are being associated microbes or affected site of the host (Fig. 1).7 17 freed from the misery and disability that have kept populations Approximately 40 million people suffer from the stigmatizing mired in poverty, generation aer generation, for centuries”, and disabling clinical manifestations of the LF among whom 15 according to Dr Margaret Chan, Director-General, World Health million have lymphoedema (elephantiasis), and particularly 25 Organization.1 million men have urogenital swelling, principally scrotal A variety of NTDs have received less attention globally. hydrocele.2 Among these, vector-borne lariasis is one of the oldest, most Lymphatic lariasis (LF) is endemic in ve of the six WHO debilitating, disabling and disguring of the NTDs. Vector- regions. Worldwide, 1.39 billion people require preventive borne lariasis has a low rate of mortality, but a high chemotherapy. Currently, 877 million people from 9 countries morbidity rate, which results in social stigma.2–4 According to (63–65% of the global population at risk) in the South-East Asia Creative Commons Attribution 3.0 Unported Licence. estimates, about 120 million people in 81 countries are Region and 432 million people from 39 countries (31% of the currently infected, and 1.34 billion people who live in areas global population at risk) in the Africa Region account for the endemic to lariasis are at risk of infection.2 Its two major maximum global burden of this disease and require preventive forms are lymphatic lariasis (LF) (responsible vector: mosquito treatment. The South-East Asia Region also accounts for species) and onchocerciasis, also known as river blindness approximately 57% of total global burden of disability adjusted (responsible vector: black y). In human beings these parasites life years (DALYs) lost due to LF. From the Western Pacic reside in lymph nodes, in deep connective, cutaneous and Region, almost 40 million people are at a risk of infection and subcutaneous tissues or in mesenteries.1,4 Severe symptoms account for 3% of the global population at risk. This region is logistically divided into two regions viz. the Mekong-Plus region This article is licensed under a generally start to appear during adulthood and are found more commonly in men than in women. These symptoms include and the Pacic region. Brunei Darussalam, the Philippines, Lao damage to various tissues such as lymphatic system, arms, legs People's Democratic Republic, Malaysia, Cambodia, and Viet- nam are 6 endemic countries in the Mekong-Plus sub region Open Access Article. Published on 11 April 2017. Downloaded 9/29/2021 12:30:02 AM. Abhishek A. Kulkarni graduated Dr Rohidas B. Arote did his PhD from Shri Bhagwan College of in gene delivery from Seoul Pharmacy, Dr Babasaheb National University, Seoul, Ambedkar Marathwada Univer- Republic of Korea in 2008. He sity, Aurangabad (MS), India in continued as a post doctoral 2013 with distinction. He fellow in the same Seoul perceived his master degree in National University for the Pharmaceutical Chemistry from period of 2009–2010. He is Y. B. Chavan College of Phar- presently working as Associate macy, Aurangabad (MS), India Professor with School of under the guidance of Dr Jai- Dentistry, Seoul National prakash N. Sangshetti with University, Republic of Korea. distinction in 2015. He has pre- His PhD research involved sented various scientic posters on topics related to Pharmaceu- development of biodegradable polymeric gene carrier system for tical Chemistry at state and national level. His area of research the treatment of various types of diseases mainly cancer. His includes design and synthesis of novel heterocyclic coupled postdoctoral research efforts focus on developing efficient gene bioactive compounds and evaluation for their antileishmanial, carriers for the treatment of lung and liver cancer. Presently, he is antimicrobial and antioxidant activities. He is also working on focusing on targeted drug and gene delivery by using multifunc- one-pot multicomponent synthesis of various bioactive molecules tional nanocarriers in the eld of nanomedicine. using various reusable catalysts. This journal is © The Royal Society of Chemistry 2017 RSC Adv.,2017,7,20628–20666 | 20629 View Article Online RSC Advances Review Fig. 1 Clinical classification of filariasis. * ¼ Hydrocele results from accumulation of straw coloured