Bioorganic & Medicinal Chemistry Letters
Synthesis of some novel phosphorylated and thiophosphorylated
benzimidazoles and benzothiazoles and their evaluation for
larvicidal potential to Aedes albopictus and Culex quinquefasciatus
Prabal Bandyopadhyay a, Manisha Sathe a, Sachin N. Tikar b, Ruchi Yadav b, Pratibha Sharma c,
Ashok Kumar c, M. P. Kaushik a,
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a Discovery Center, Process Technology Development Division, Defence Research & Development Establishment, Jhansi Road, Gwalior 474002, MP, India
b Vector Management Division, Defence Research & Development Establishment, Jhansi Road, Gwalior 474002, MP, India
c School of Chemical Sciences, Devi Ahilya University, Takshashila Campus, Khandwa Road, Indore 452001, MP, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Series of benzimidazole and benzothiazole linked phosphoramidates and phosphoramidothioates (5a–j)
and benzimidazole linked phenylphosphoramidates and phenylphosphoramidothioates (10a–e) were
synthesized. The title compounds were preliminary screened for mosquito larvicidal properties against
Aedes albopictus and Culex quinquefasciatus at different concentration from 40 to 5 mg/L. Among the
screened compounds three compounds revealed potential larvicidal effects with 100% mortality in the
order of 10e > 5j > 5e. Compound 10e was found to be the most toxic compound to Ae. albopictus and
Cx. quinquefasciatus. The LC50 of 10e against Ae. albopictus was found to be 6.42 and 5.25 mg/L at 24
and 48 h, respectively, whereas it was 7.01 and 3.88 mg/L, respectively in Cx. quinquefasciatus. Temephos
was used as positive control.
Received 25 October 2013
Revised 6 April 2014
Accepted 21 April 2014
Available online xxxx
Keywords:
Phosphoramidate/phosphoramidothioate
Benzimidazole/benzothiazole
Larvicidal activity
Ó 2014 Elsevier Ltd. All rights reserved.
Aedes albopictus
Culex quinquefasciatus
Mosquitoes are one of the deadliest insects in this planet which
create biting nuisance and also transmit deadly diseases like
malaria, filariasis, yellow fever, dengue, chikungunya and Japanese
encephalitis, which contribute significantly to economic loss and
social debility in tropical countries, causing millions of death every
year.1 Mosquitoes in the genus Aedes are responsible for the
transmission of yellow fever, dengue, chikungunya and other
pathogenic arbo-viruses.2 Similarly, Culex quinquefasciatus com-
monly known as southern house mosquito and act as a primary
vector of lymphatic filariasis with worldwide distribution.3Cx.
quinquefasciatus commonly inhabit around human dwellings and
on aging prefer to bite humans than other mammals. It is an
important vector of lymphatic Filariasis caused by nematodes such
as Wuchereria bancrofti and Brugia malayi in humans in some parts
of India. Globally over 100 million individuals are affected due to
Filariasis annually. Out of which approximately 43 million Filariasis
cases results into serious disability and disfiguring of limbs.4
resistance, and undesirable effects on non-target organisms.5
These problems have highlighted the need of new strategies for
mosquito control.
The best way to prevent outbreaks of mosquito-borne disease is
to control the vector at the grass root level. However, the control of
mosquito borne diseases is becoming increasingly difficult because
of effectiveness of vector control tools has declined due to the
development of resistance in mosquitoes against currently used
insecticides.6 Vector control strategy7 is an important part of the
global disease control programme. The objective behind this is to
reduce the levels of mortality and morbidity by reducing transmis-
sion of the disease. Therefore, the best way to prevent the out-
breaks of mosquito-borne disease is to control the mosquito
vector at the larval stage itself. Mosquitoes in the larval stage are
attractive targets for pesticides due to their stationary nature they
can be easily targeted in breeding habitats. Many organophospho-
rus (OP) compounds like reldan, temephos, fenthion, chlorpyrifos,
pirimiphos-methyl etc. have been in use for controlling Cx. quin-
quefasciatus, the vector of bancroftian filariasis in many countries.8
Recently, in the interest of developing a more effective insecticide
novel classes of organophosphorous compounds have been synthe-
sized and screened against their larvae and the adult mosquitos.9
The chemistry of organophosphorus (OP) compounds is a
rapidly developing area of research because of their importance
Repeated use of synthetic insecticides for mosquito control has
fostered several environmental and human health concerns,
including disruption of natural biological control systems, resur-
gences in mosquito populations, widespread development of
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Corresponding author. Tel.: +91 751 2343972; fax: +91 751 2340042.
0960-894X/Ó 2014 Elsevier Ltd. All rights reserved.