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Pharmacological Significance of Heterocyclic 1H-Benzimidazole

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Pharmacological Significance of Heterocyclic 1H-Benzimidazole Tahlan et al. BMC Chemistry (2019) 13:101 https://doi.org/10.1186/s13065-019-0625-4 BMC Chemistry REVIEW Open Access Pharmacological signifcance of heterocyclic 1H-benzimidazole scafolds: a review Sumit Tahlan, Sanjiv Kumar and Balasubramanian Narasimhan* Abstract Heterocyclic compounds are inevitable in a numerous part of life sciences. These molecules perform various note- worthy functions in nature, medication and innovation. Nitrogen-containing heterocycles exceptionally azoles family are the matter of interest in synthesis attributable to the way that they happen pervasively in pharmacologically dynamic natural products, multipurpose arranged useful materials also profoundly powerful pharmaceuticals and agrochemicals. Benzimidazole moiety is the key building block for several heterocyclic scafolds that play central role in the biologically functioning of essential molecules. They are considered as promising class of bioactive scafolds encompassing diverse varieties of activities like antiprotozoal, antihelminthic, antimalarial, antiviral, anti-infammatory, antimicrobial, anti-mycobacterial and antiparasitic. Therefore in the present review we tried to compile the various pharmacological activities of diferent derivatives of heterocyclic benzimidazole moiety. Keywords: Benzimidazole derivatives, Antiprotozoal activity, Anti-infammatory activity, Antimalarial activity, Antimycobacterial activity, Antiviral activity, Anticancer activity Introduction acetylcholinesterase [4], antiprotozoal [5], anti-infam- Among heterocyclic pharmacophores, the benzimida- matory [6], analgesic [7], antihistaminic [8], antimalarial zole ring system is quite common. Tese substructures [9], antitubercular [10], anti-HIV [11] and antiviral [12]. are often called ‘privileged’ due to their wide recurrence Some of the already synthesized compounds from the in bioactive compounds [1]. Benzimidazole moiety is above mentioned feld have found very strong application a fusion of benzene and imidazole ring system at the 4 in medicine praxis. Te activity against bacteria, fungi and 5 positions of imidazole ring. Tey have properties of and helminthes resulted their mode of action, which both acids and bases. Te NH group here is highly acidic resulted in the blockage of microtubule in various nema- and also feebly basic. Another feature of it is that they tode, trematode and cystode [13]. Benzimidazole-based comprise the ability to form salts. Te benzimidazole drugs exhibit a wide range of diferent biological activi- moiety is useful for the development of novel medicinal ties as a result of changing the groups on the core struc- compounds in pharmaceutical feld. Benzimidazole is ture. Some marketed drugs containing benzimidazole also a vital pharmacophore, a privileged sub-structure in nucleus are shown in Fig. 1. medicinal chemistry which contributes as a key part for Acetylcholinesterase (AChE) is a core chemical diferent natural activities [2]. engaged with the ending of nerve signs via the hydroly- sis of acetylcholine. It is an objective of medication Pharmacological signifcance of benzimidazole derivatives advancement to battle the neuromuscular issue, for Literature survey reveals that the various derivatives of example, glaucoma, myasthenia gravis and Alzheimer’s benzimidazole have been synthesized for their pharmaco- disease (AD). AChE has been focused in the cure of AD, logical activities such as antimicrobial [3], anticancer [2], a dynamic neurodegenerative disease portrayed by neu- rofbrillary tangles, β-amyloid plaques and loss of focal *Correspondence: [email protected] cholinergic ability. A lack in cholinergic neurotransmis- Faculty of Pharmaceutical Sciences, Maharshi Dayanand University, sion is viewed as one of the real reasons for reminis- Rohtak 124001, India cence weaknesses in the patients with AD. One of the © The Author(s) 2019. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creat iveco mmons .org/licen ses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/ publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Tahlan et al. BMC Chemistry (2019) 13:101 Page 2 of 21 Albendazole Nocodazole Veliparib (Antiprotozoal) (Anticancer) (Anticancer) Lerisetron Adibenden Maribavir (Antihistaminic) (Phoshodiesterase inhibitor) (Antiviral) Fig. 1 Some benzimidazoles containing medicinal preparation compelling methodologies for improving the choliner- fever, flariasis, chikungunya, encephalitis and dengue. gic transmission is to utilize the inhibitors of acetylcho- Mosquitoes in the class Aedes are liable for the trans- linesterase [4]. Parasitic ailments are as yet overall issues mission of chikungunya, dengue, yellow fever and other that deeply afect general wellbeing. Contaminations pathogenic arbo-infections. Likewise, the prime vector brought about by protozoa, for example, Trypanosoma for lymphatic flariasis is Culex quinquefasciatus, as well cruzi, Plasmodium falciparum, Entamoeba histolytica, called southern house mosquito. Cx. quinquefasciatus Leishmania Mexicana, Trichomonas vaginalis, Giardia ordinarily stay around human lodging and on maturing intestinalis and helminth, for example, Taenia solium or like to nibble people than diferent warm blooded crea- Trichinella spiralis are overall spread ailments that infu- tures. Intestinal sickness is a mosquito-borne infectious ence predominantly immature nations, where tropical or ailment which is mostly transmitted by a contaminated template temperatures exist, yet in addition poor uncon- female Anopheles mosquito [15]. taminated and cleanliness conditions are normal [14]. Tuberculosis (TB), which is caused prevalently by Irritation is a confned reaction of body tissues to destruc- Mycobacterium tuberculosis (Mtb), is the main source of tive incentives or injures bringing about the arrangement of death from a reparable irresistible ailment, and has been protein-rich exudates. It is a defensive reaction of the non- recognized by the World Health Organization (WHO) as specifc resistant framework that expels the essential driver one of the three need illnesses for medication innovative of cell damage; eradicate necrotic cells and tissues harmed work [16]. Viral hemorrhagic fever is a genuine sickness from the incendiary procedure and commence tissue repair. portrayed by broad vascular harm and draining diathesis, Te essential indications of aggravation are redness, heat, fever and various organ inclusions. Various infections torment, swelling and loss of capacity. Reason for aggra- can cause this disorder, each with its very own creature vation is physical as well chemical means, immunologi- repository, method of transmission, mortality rate, and cal responses and contamination by pathogenic life form. clinical result in people [17]. Aggravation can be assigned as acute and chronic. Acute Worldwide infectious disease fgures have attained an irritation is described by the exudation of liquid and plasma alarming level following the proliferation of Gram-pos- proteins (oedema) and the development of leukocytes, par- itive and Gram-negative multi-drug-resistant species. ticularly neutrophils. Chronic irritation is otherwise called Patient non-compliance and the occurrence of multidrug- constant aggravation, in which tissue destruction and recov- resistant pathogens often interfere innovative infection ering are continuing all the while, for example, tuberculosis, therapies that depend on a sustained multidrug course. rheumatoid joint infammation, constant lung infections Rational drug design has been shown to be very benefcial and atherosclerosis [6]. in this respect, since the biochemical basis of intrinsic and Mosquitoes are one of the deadliest creepy crawlies in acquired resistance mechanisms is largely known [3]. earth which generate biting irritation and also transmit One of the most commonly known gastrointestinal lethal infections, for example, intestinal sickness, yellow malignancies is colorectal tumor (CRC). Alterations Tahlan et al. BMC Chemistry (2019) 13:101 Page 3 of 21 in lifestyle, elevated-fat diet, physiological disillusion- derivatives, compounds 1a and 1b were found to be the ment and smoking are associated to pathogenesis of most active against eeAChE and hAChE using tacrine as CRC. Approximately 25% of CRC cases were identifed standard drug (Table 1, Fig. 3) [4]. with early analysis metastases and at some stage of life Yoon et al. synthesized a class of benzimidazoles nearly 50% of CRC patients would sufer from metastasis. and screened for its acetylcholinesterase and butyryl- Te therapy results for these patients are largely unsat- cholinesterase inhibitor activity. Compound 2a isfactory as normal regimens consider the possibility of (Fig. 3) showed promising inhibitory activity with homogeneous tumor mass distribution [2]. IC50 = 5.12 µM for BChE and IC50 = 8.63 µM for AChE Rational designed based on literature survey of benzi- using rivastigmine and donepezil (22.00, 7.95 µM for midazole derivatives is shown in Fig. 2. BChE and 50.20, 0.03 µM for AChE) as standard [18]. Reported pharmacological activities Antiprotozoal activity of benzimidazole derivatives Andrzejewska et al.
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