Reproductive
health research in CDRI focuses on female
and male contraceptives, spermicides with
anti-STI properties, agents for the management
of osteoporosis, cancer breast and benign
prostatic hyperplasia.
Global population is projected to rise exponentially from the current ~6 billion to 9 billion in 2050. Indian population, which contributes to one sixth of present world population, is expected to touch 1264 million in 2016. According to the World Health Organization, the family planning needs of more than 120 million couples goes unmet every year resulting in an annual abortion rate of 46 million. Most of these abortions take place in developing countries under unsafe and insanitary conditions causing the death of 68000 women per year. The Ministry of Health and Family Welfare, Government of India is supporting a long-term innovative Reproductive Health Research Program with focus on contraceptive development at the Central Drug Research Institute, Lucknow. In addition, given increased longevity, particularly among women, postmenopausal disorders including osteoporsis and breast cancers occur more frequently. The overall objectives of the program are to design and synthesize novel molecules/isolate from natural sources and bioevaluate them for generating new leads and to develop them as female or male contraceptives, spermicides with anti-STI properties, agents for the management of osteoporosis, breast cancer and benign prostatic hyperplasia, evaluate traditional remedies for fertility regulation and endocrine disorders, understand mode of action of promising agents and undertake basic research to generate new knowledge on male and female reproductive endocrinology relevant to fertility regulation and endocrine disorders.
BASIC RESEARCH
Objective:
To generate new knowledge on male and female
reproductive endocrinology relevant to fertility
regulation and endocrine disorders due to
menopause and andropause.
•
Novel antispermatogenic compounds targeting Sertoli cell functions, male germ cell tight junctions and study of ubiquitin mediated protein degradation pathway in male contraception
•
Studies on male infertility – protective effect of shilajit against cadmium induced infertility in male mice.
•
To develop osteogenic (bone forming) molecules and preparations.
•
Studies on antiproliferative action of 2,3-diaryl-2H-1- benzopyran derivative in human endometrial cancer cells (Ishikawa cells) and human BPH-derived prostatic stromal cells.
•
Naturally-derived naphthaquinone compounds induce apoptosis of prostate and endometrial cancer cells: mechanism of action studies; novel SERMs for management of BPH.
•
Triaryl pyranones as a potential new class of anti-breast cancer agents
Drug design and synthesis
•
Synthetic chalcone-based beta adrenergic receptor modulators to elicit transient PTH stimulation as a way to enhance osteoblast function.
•
Following leads from some natural compounds to stimulate bone morphogenic proteins production by osteoblasts, benzofurochomenes are being developed as rapid fracture healing agents.
•
A newly discovered novel compound, dihydroflavone glycoside, from terrestrial plant source as bone anabolic agent for the treatment of postmenopausal osteoporosis.
•
Disulfide esters of carbothioic acid, benzenepropanamine analogues and carbodithioic acid derivaties are being designed for selectively targeting sulfhydryl groups on human sperm surface that render membrane fluidity which is essential for motility and normal physiology.
•
Imidazolophenoxyphenylpropyl amines are envisaged to introduce antimicrobial activity in spermicidal scaffolds for developing microbicidal contraceptives for vaginal use.
•
Pyranoquinoline derivatives as novel agents for management of BPH through estrogen receptor mediated pathway.
•
3,4,6-triaryl-2-pyranones and 2,3,4-triarylbenzopyran derivatives as a new class of therapeutic agent for breast cancer.
Screening and drug development
•
Design and synthesis of new and novel non-steroidal molecules for post-coital contraceptive efficacy; collection and bioevaluation of medicinal plants for anti-implantation activity and follow-up studies on promising agents.
•
Development of safe and effective contraceptives that exert action on testis (spermiogenesis), epididymis (sperm maturation/fertilization) or on sperm (spermicidal).
•
Designing novel drugs and formulations for use as dual protection vaginal contraceptives for protection against unwanted pregnancy and STDs/STIs.
•
Screening and development of natural and synthetic compounds having osteoblast promoting functions in vitro and bone anabolic effect in vivo.
•
Developing agents exhibiting potent anti-proliferative activity, but being free from estrogen-related health hazards, for the management of breast cancer.
•
Establishment of test systems for screening of synthetic compounds/natural products against BPH and mechanism of action studies with active agents on proliferative and apoptotic indices and other parameters in prostatic tissue.
•
Developing agents for prevention of estrogen deficiency and age related bone loss, but lacking carcinogenic effect of estrogen on the endometrium and breast, in addition to being free from other estrogen-related health hazards
Significant achievements
•
Centchroman*, the world's first non-steroidal weekly oral contraceptive.-
Licensed to Industry
•
Consap*, a herbal intravaginal contraceptive cream containing "Reetha" saponins as spermicide.-
Licensed to Industry
•
Isaptent, an aid for medical termination of pregnancy developed by utilizing "Isapgol" seed husk.
•
Centchroman for the management of dysfunctional uterine bleeding.
•
Compound CDRI-99/373 (a new antiosteoporosis/anti-resorptive agent)
•
Several other promising new drug candidates for osteoporosis (osteogenic agents) and vaginal contraception are under advanced stages of pre-clinical development.
Recent Publications
•
Trivedi R, Kumar A, Gupta V, Kumar S, Nagar GK, Romero JR, Dwivedi AK, Chattopadhyay N. Effects of Egb 761 on bone mineral density, bone microstructure, and osteoblast function: Possible roles of quercetin and kaempferol. Mol Cell Endocrinol. 2009;302(1):86-91.
•
Bhargavan B, Gautam AK, Singh D, Kumar A, Chaurasia S, Tyagi AM, Yadav DK, Mishra JS, Singh AB, Sanyal S, Goel A, Maurya R, Chattopadhyay N. Methoxylated isoflavones, cajanin and isoformononetin, have non-estrogenic bone forming effect via differential mitogen activated protein kinase (MAPK) signaling. J Cell Biochem. 2009;108(2):388-99.
•
Jain RK, Jain A, Maikhuri JP, Sharma VL, Dwivedi AK, Kumar ST, Mitra K, Bajpai VK, Gupta G. In vitro testing of rationally designed spermicides for selectively targeting human sperm in vagina to ensure safe contraception. Hum Reprod. 2009;24(3):590-601.
•
Jain RK, Maikhuri JP, Kiran Kumar ST, Sharma VL, Dwivedi AK, Mitra K, Bajpai VK, Gupta G. Novel disulphide esters of carbothioic acid as potent, non-detergent spermicides with low toxicity to Lactobacillus and HeLa cells in vitro. Hum Reprod. 2007;22(3):708-16.
•
Daverey A, Saxena R, Tewari S, Goel SK, Dwivedi A. Expression of estrogen receptor co-regulators SRC-1, RIP140 and NCoR and their interaction with estrogen receptor in rat uterus, under the influence of ormeloxifene. J Steroid Biochem Mol Biol. 2009;116(1-2):93-101.
•
Srinivasan KR, Blesson CS, Fatima I, Kitchlu S, Jain SK, Mehrotra PK, Dwivedi A. Expression of alphaVbeta3 integrin in rat endometrial epithelial cells and its functional role during implantation. Gen Comp Endocrinol. 2009;160(2):124-33.
•
Madhukar D, Rajender S. Hormonal treatment of male infertility: promises and pitfalls. J Androl. 2009;30(2):95-112.
•
Rituraj Konwar, Preeti Chaudhary, Sandeep Kumar, Deepti Mishra, Naibedya Chattopadhyay, Hemant Kumar Bid. Breast Cancer Risk Associated with Polymorphisms of IL-1RN and IL-4 Gene in Indian Women. Oncology Research2009;17(8):367-72.
•
Rawat P, Kumar M, Sharan K, Chattopadhyay N, Maurya R Ulmosides A and B: flavonoid 6-C-glycosides from Ulmuswallichiana, stimulating osteoblast differentiation assessed by alkaline phosphatase. Bioorg Med Chem Lett. 2009;19(16):4684-7.
•
Kiran Kumar ST, Kumar L, Sharma VL, Jain A, Jain RK, Maikhuri JP, Kumar M, Shukla PK, Gupta G. Carbodithioic acid esters of fluoxetine, a novel class of dual-function spermicides. Eur J Med Chem. 2008;43(10):2247-56.
Best viewed
at 800 X 600 Resolutions | Internet
Explorer 5.0 - Later Version
<%
if session("iNumber")="" then
'conn.open mydsn
Dim rsHits
Set rsHits=Server.CreateObject("ADODB.Recordset")
rsHits.CursorLocation=adUseClient
rsHits.Open "Select visits from Hits", conn, adOpenKeyset, adLockOptimistic
session("iNumber")=rsHits("visits") + 1
rsHits("visits")=rsHits("visits") + 1
rsHits.Update
rsHits.Close
set rsHits=Nothing
end if
If Len(session("iNumber")) > 0 then
'Display iNumber
Response.Write "
" & ConstructDigits(session("iNumber")) & "
"
End If
''''
Function ConstructDigits(iValue)
'This function accepts a single parameter, iValue, and
'returns HTML containing a series of images representing
'a graphical image of the value in iValue
'Start by ensuring iValue is a number
If Not IsNumeric(iValue) then
ConstructDigits = iValue & " IS NOT A NUMBER!"
Exit Function
End If
'Can't show decimals!
If InStr(1, iValue, ".") then
ConstructDigits = "CANNOT CONTAIN DECIMALS!"
Exit Function
End If
'Can't show negative numbers!
If iValue < 0 then
ConstructDigits = "CANNOT DISPLAY NEGATIVE NUMBERS!"
Exit Function
End If
Dim iLoop, strResults
For iLoop = (Len(iValue) - 1) to 0 STEP -1
strResults = strResults & ""
Next
ConstructDigits = strResults
End Function
''''
%>
